SummaryRNA viruses have extreme mutation frequencies. When a RNA virus replicates, nucleotide mutations are generated resulting in a population of variants. This genetic diversity creates a cloud of mutations that are potentially beneficial to viral survival, but the majority of mutations are detrimental to the virus. By increasing the mutation rate of a RNA virus, viral fitness is reduced because it generates more errors, and attenuates the virus during in vivo infection. Another feature that affects RNA virus fitness is mutational robustness. Mutational robustness is the ability to buffer the negative effects of mutation.
The attenuation of RNA viruses for vaccine production faces problems of genetic instability and reversion to a pathogenic phenotype. The conventional method for attenuation is mostly empirical and specific to the particular RNA virus species. Hence, it cannot be universally applied to a variety of virus types. We've developed a non-empirical, rational means of attenuating RNA viruses, targeting mutational robustness as modifiable trait. We demonstrate that mutational robustness of RNA viruses can be modified without changing a virus' physical and biological properties for vaccine production; yet the virus is attenuated as it becomes victim of its naturally high mutation rate. Specifically, the genome of RNA viruses are modified so that a larger proportion of mutations become lethal Stop mutations. Our technology places the virus one step away from these Stop mutations (1-to-Stop). We succeeded in attenuating two RNA viruses from very different viral families, confirming the broad applicability of this approach. These viruses were attenuated in vivo, generated high levels of neutralizing antibody and protected mice from lethal challenge infection.
The proposal now seeks to complete proof of concept studies and develop commercialization strategies to scale up this new technology to preclinical testing with industrial partners.

RNA viruses have extreme mutation frequencies. When a RNA virus replicates, nucleotide mutations are generated resulting in a population of variants. This genetic diversity creates a cloud of mutations that are potentially beneficial to viral survival, but the majority of mutations are detrimental to the virus. By increasing the mutation rate of a RNA virus, viral fitness is reduced because it generates more errors, and attenuates the virus during in vivo infection. Another feature that affects RNA virus fitness is mutational robustness. Mutational robustness is the ability to buffer the negative effects of mutation.
The attenuation of RNA viruses for vaccine production faces problems of genetic instability and reversion to a pathogenic phenotype. The conventional method for attenuation is mostly empirical and specific to the particular RNA virus species. Hence, it cannot be universally applied to a variety of virus types. We've developed a non-empirical, rational means of attenuating RNA viruses, targeting mutational robustness as modifiable trait. We demonstrate that mutational robustness of RNA viruses can be modified without changing a virus' physical and biological properties for vaccine production; yet the virus is attenuated as it becomes victim of its naturally high mutation rate. Specifically, the genome of RNA viruses are modified so that a larger proportion of mutations become lethal Stop mutations. Our technology places the virus one step away from these Stop mutations (1-to-Stop). We succeeded in attenuating two RNA viruses from very different viral families, confirming the broad applicability of this approach. These viruses were attenuated in vivo, generated high levels of neutralizing antibody and protected mice from lethal challenge infection.
The proposal now seeks to complete proof of concept studies and develop commercialization strategies to scale up this new technology to preclinical testing with industrial partners.

SummaryThe project aims to create a demo system for cost effective, non-invasive device for rapid detection of cystic fibrosis in humans. The detection of human recessive diseases has been dominated by the use of fluorescent biomarkers, based on organic dyes, helping researchers to study and analyse gene expression, cell cycle, and enzymatic activity. Among several proteolytic enzymes, trypsin has attracted much attention, as it is a target in the study of various important human recessive diseases including, for example, cystic fibrosis (CF).
We present herein two colour encoded silica nanospheres (2nanoSi) for the fluorescence quantitative ratiometric determination of cystic in humans. Current detection technologies for cystic fibrosis diagnosis are slow, costly and suffer from false positives. The 2nanoSi proved to be a fast (minutes), a single-step and with two times higher sensitivity than the state-of-the-art biomarkers based sensors for cystic fibrosis, allowing the quantification of trypsin concentrations in a wide range (25-350 μg/L). Moreover, our approach can be used from the 4th day of life when the trypsin concentration is already the same as in adults. Furthermore, as trypsin is directly related to the development of cystic fibrosis (CF), different human phenotypes, i.e. normal (160-340 μg/L), CF homozygotic (0-90 μg/L), and CF heterozygotic (91-349 μg/L), respectively, can be determined using our 2nanoSi nanospheres. We anticipate the 2nanoSi system to be a starting point for non-invasive, easy-to-use and cost effective ratiometric fluorescence biomarker for recessive genetic diseases alike human cystic fibrosis.

The project aims to create a demo system for cost effective, non-invasive device for rapid detection of cystic fibrosis in humans. The detection of human recessive diseases has been dominated by the use of fluorescent biomarkers, based on organic dyes, helping researchers to study and analyse gene expression, cell cycle, and enzymatic activity. Among several proteolytic enzymes, trypsin has attracted much attention, as it is a target in the study of various important human recessive diseases including, for example, cystic fibrosis (CF).
We present herein two colour encoded silica nanospheres (2nanoSi) for the fluorescence quantitative ratiometric determination of cystic in humans. Current detection technologies for cystic fibrosis diagnosis are slow, costly and suffer from false positives. The 2nanoSi proved to be a fast (minutes), a single-step and with two times higher sensitivity than the state-of-the-art biomarkers based sensors for cystic fibrosis, allowing the quantification of trypsin concentrations in a wide range (25-350 μg/L). Moreover, our approach can be used from the 4th day of life when the trypsin concentration is already the same as in adults. Furthermore, as trypsin is directly related to the development of cystic fibrosis (CF), different human phenotypes, i.e. normal (160-340 μg/L), CF homozygotic (0-90 μg/L), and CF heterozygotic (91-349 μg/L), respectively, can be determined using our 2nanoSi nanospheres. We anticipate the 2nanoSi system to be a starting point for non-invasive, easy-to-use and cost effective ratiometric fluorescence biomarker for recessive genetic diseases alike human cystic fibrosis.

Max ERC Funding

150 000 €

Duration

Start date: 2015-04-01, End date: 2016-09-30

Project acronym2D-Ink

ProjectInk-Jet printed supercapacitors based on 2D nanomaterials.

Researcher (PI)Valeria Nicolosi

Host Institution (HI)THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

Call DetailsProof of Concept (PoC), PC1, ERC-2014-PoC

SummaryThis proposal will determine the technical-economic viability of scaling-up ultra-thin, ink-jet printed films based on liquid-phase exfoliated single atomic layers of a range of nanomaterials. The PI has developed methods to produce in liquid nanosheets of a range of layered materials such as graphene, transition metal oxides, etc. These 2D-materials have immediate and far-reaching potential in several high-impact technological applications such as microelectronics, composites and energy harvesting and storage. 2DNanoCaps (ERC ref: 278516) has demonstrated that lab-scale ultra-thin graphene-based supercapacitor electrodes result in unusually high-power and extremely long device life-time (100% capacitance retention for 5000 charge-discharge cycles at the high power scan rate of 10,000 mV/s). This performance is an order of magnitude better than similar systems produced with conventional methods which cause materials restacking and aggregation. A following ERC PoC grant (2D-USD, Project-Number 620189) is currently focussed on up-scaling the production of thin-films deposition methods based on ultrasonic spray for the production of large-area electrodes for supercapacitors applications. In this proposal we want to explore the new concept of manufacturing conductive, robust, thin, easily assembled electrode and solid electrolytes to realize highly-flexible and all-solid-state supercapacitors by ink-jet printing. This opportunity is particularly relevant to the electronics and portable-device industry and offers the possibility to solve flammability issues, maintaining light weight, flexibility, transparency and portability. In order to do so it will be imperative to develop ink-jet printing methods and techniques. We believe our combination of unique materials and cost-effective, robust and production-scalable process of ultra- thin ink-jet printing will enable us to compete for significant global market opportunities in the energy-storage space.

This proposal will determine the technical-economic viability of scaling-up ultra-thin, ink-jet printed films based on liquid-phase exfoliated single atomic layers of a range of nanomaterials. The PI has developed methods to produce in liquid nanosheets of a range of layered materials such as graphene, transition metal oxides, etc. These 2D-materials have immediate and far-reaching potential in several high-impact technological applications such as microelectronics, composites and energy harvesting and storage. 2DNanoCaps (ERC ref: 278516) has demonstrated that lab-scale ultra-thin graphene-based supercapacitor electrodes result in unusually high-power and extremely long device life-time (100% capacitance retention for 5000 charge-discharge cycles at the high power scan rate of 10,000 mV/s). This performance is an order of magnitude better than similar systems produced with conventional methods which cause materials restacking and aggregation. A following ERC PoC grant (2D-USD, Project-Number 620189) is currently focussed on up-scaling the production of thin-films deposition methods based on ultrasonic spray for the production of large-area electrodes for supercapacitors applications. In this proposal we want to explore the new concept of manufacturing conductive, robust, thin, easily assembled electrode and solid electrolytes to realize highly-flexible and all-solid-state supercapacitors by ink-jet printing. This opportunity is particularly relevant to the electronics and portable-device industry and offers the possibility to solve flammability issues, maintaining light weight, flexibility, transparency and portability. In order to do so it will be imperative to develop ink-jet printing methods and techniques. We believe our combination of unique materials and cost-effective, robust and production-scalable process of ultra- thin ink-jet printing will enable us to compete for significant global market opportunities in the energy-storage space.

Host Institution (HI)THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

Call DetailsProof of Concept (PoC), PC1, ERC-2013-PoC

SummaryThis proposal will determine the technical and economic viability of scaling up ultra-thin film deposition processes for exfoliated single atomic layers.
The PI has developed methods to produce exfoliated nanosheets from a range of layered materials such as graphene, transition metal chalcogenides and transition metal oxides. These 2D materials have immediate and far-reaching potential in several high-impact technological applications such as microelectronics, composites and energy harvesting and storage.
2DNanoCaps (ERC ref: 278516) has already demonstrated that lab-scale ultra-thin graphene-based supercapacitor electrodes for energy storage result in unusually high power performance and extremely long device life-time (100% capacitance retention for 5000 charge-discharge cycles at the high power scan rate of 10,000 mV/s). This performance is remarkable- an order of magnitude better than similar systems produced with more conventional methods, which cause materials restacking and aggregation. 2D nanosheets also offer the chance of exploring the unique possibility of manufacturing conductive, robust, thin, easily assembled electrode and solid electrolytes to realize highly flexible and all-solid-state supercapacitors. This opportunity is particularly relevant from the industrial point of view especially in relation to the flammability issues of the electrolytes used for commercial energy storage devices at present.
In order to develop and exploit any of the applications listed above, it will be imperative to develop deposition methods and techniques capable of obtaining industrial-scale “sheet-like” coverage, where flake re-aggregation is avoided.
We believe our combination of unique material properties and cost effective, robust and production-scalable process of ultra-thin deposition will enable us to compete for significant global market opportunities in the energy-storage space

This proposal will determine the technical and economic viability of scaling up ultra-thin film deposition processes for exfoliated single atomic layers.
The PI has developed methods to produce exfoliated nanosheets from a range of layered materials such as graphene, transition metal chalcogenides and transition metal oxides. These 2D materials have immediate and far-reaching potential in several high-impact technological applications such as microelectronics, composites and energy harvesting and storage.
2DNanoCaps (ERC ref: 278516) has already demonstrated that lab-scale ultra-thin graphene-based supercapacitor electrodes for energy storage result in unusually high power performance and extremely long device life-time (100% capacitance retention for 5000 charge-discharge cycles at the high power scan rate of 10,000 mV/s). This performance is remarkable- an order of magnitude better than similar systems produced with more conventional methods, which cause materials restacking and aggregation. 2D nanosheets also offer the chance of exploring the unique possibility of manufacturing conductive, robust, thin, easily assembled electrode and solid electrolytes to realize highly flexible and all-solid-state supercapacitors. This opportunity is particularly relevant from the industrial point of view especially in relation to the flammability issues of the electrolytes used for commercial energy storage devices at present.
In order to develop and exploit any of the applications listed above, it will be imperative to develop deposition methods and techniques capable of obtaining industrial-scale “sheet-like” coverage, where flake re-aggregation is avoided.
We believe our combination of unique material properties and cost effective, robust and production-scalable process of ultra-thin deposition will enable us to compete for significant global market opportunities in the energy-storage space

Max ERC Funding

148 021 €

Duration

Start date: 2014-01-01, End date: 2014-12-31

Project acronym2DIR SPECTROMETER

ProjectA step-change in sensitivity for two dimensional laser infrared spectroscopy

Researcher (PI)Jasper VAN THOR

Host Institution (HI)IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE

Call DetailsProof of Concept (PoC), PC1, ERC-2013-PoC

Summary"Here, we propose a novel design for a significantly improved detector for the emerging field of coherent two-dimension infrared (2DIR) spectroscopy, which is an optical analog of Nuclear Magnetic Resonance spectroscopy (NMR). 2DIR is a cutting edge technique which is rapidly growing and has applications in subjects as diverse as energy sciences, biophysics, biomedical research and physical chemistry. Currently, the single most important technical problem that is generally agreed to limit applications of the methodology is the sensitivity with which the signals are measured. Having worked on multiple stabilisation techniques during the ERC funded research it was realised that a straightforward design alteration of the infrared detector will improve the sensitivity very significantly, theoretically by more than one order of magnitude. Here, the technical principles are explained, and a plan for commercialising the instrument in collaboration with the current market leader - Infrared System Development Corp. (ISDC) -. We apply for funding to develop the prototype."

"Here, we propose a novel design for a significantly improved detector for the emerging field of coherent two-dimension infrared (2DIR) spectroscopy, which is an optical analog of Nuclear Magnetic Resonance spectroscopy (NMR). 2DIR is a cutting edge technique which is rapidly growing and has applications in subjects as diverse as energy sciences, biophysics, biomedical research and physical chemistry. Currently, the single most important technical problem that is generally agreed to limit applications of the methodology is the sensitivity with which the signals are measured. Having worked on multiple stabilisation techniques during the ERC funded research it was realised that a straightforward design alteration of the infrared detector will improve the sensitivity very significantly, theoretically by more than one order of magnitude. Here, the technical principles are explained, and a plan for commercialising the instrument in collaboration with the current market leader - Infrared System Development Corp. (ISDC) -. We apply for funding to develop the prototype."

SummarySome 50% of human melanoma tumors have activating mutations in the BRAF gene. BRAF inhibitor drugs given either alone or in combination with MEK inhibitors have improved progression-free and overall survival in patients with BRAF mutant metastatic melanoma. However, drug resistance invariably limits the duration of clinical benefit of such treatments and is almost always associated with re-activation of signaling through the MAP kinase pathway in the presence of drug due to secondary mutations in the pathway. This highlights the urgent need to develop strategies to treat melanomas that have developed resistance to BRAF and/or MEK inhibitors.
As part of an ERC advanced grant, my laboratory has shown that BRAF inhibitor withdrawal in melanomas that have developed resistance to BRAF inhibitors leads to a transient growth arrest that is the consequence of temporary hyperactivation of signaling through the MAP kinase pathway, explaining the so called “drug holiday effect”. We have also found that subsequent treatment of such BRAF inhibitor resistant melanomas with Histone DeACetylase inhibitor drugs (HDACi) leads to persistent hyperactivation of MAP kinase signaling, causing both chronic proliferation arrest and cell death, ultimately leading to complete regression of BRAF-inhibitor resistant melanomas in mice.
We propose here to perform a proof of concept study in at least 10 evaluable melanoma patients that, after proven initial tumor response, have developed resistance to BRAF inhibitors to validate that subsequent treatment of such patients with an HDACi drug will result in durable responses. Translational studies on tumor biopsies taken before, during and after HDACi treatment will be performed to study the cellular effects of HDACi treatment. Our goal is to provide initial proof of concept in patients for use of this sequential BRAFi-HDACi therapy as the treatment of choice for the some 40,000 BRAF mutant melanomas that are diagnosed in the EU annually.

Some 50% of human melanoma tumors have activating mutations in the BRAF gene. BRAF inhibitor drugs given either alone or in combination with MEK inhibitors have improved progression-free and overall survival in patients with BRAF mutant metastatic melanoma. However, drug resistance invariably limits the duration of clinical benefit of such treatments and is almost always associated with re-activation of signaling through the MAP kinase pathway in the presence of drug due to secondary mutations in the pathway. This highlights the urgent need to develop strategies to treat melanomas that have developed resistance to BRAF and/or MEK inhibitors.
As part of an ERC advanced grant, my laboratory has shown that BRAF inhibitor withdrawal in melanomas that have developed resistance to BRAF inhibitors leads to a transient growth arrest that is the consequence of temporary hyperactivation of signaling through the MAP kinase pathway, explaining the so called “drug holiday effect”. We have also found that subsequent treatment of such BRAF inhibitor resistant melanomas with Histone DeACetylase inhibitor drugs (HDACi) leads to persistent hyperactivation of MAP kinase signaling, causing both chronic proliferation arrest and cell death, ultimately leading to complete regression of BRAF-inhibitor resistant melanomas in mice.
We propose here to perform a proof of concept study in at least 10 evaluable melanoma patients that, after proven initial tumor response, have developed resistance to BRAF inhibitors to validate that subsequent treatment of such patients with an HDACi drug will result in durable responses. Translational studies on tumor biopsies taken before, during and after HDACi treatment will be performed to study the cellular effects of HDACi treatment. Our goal is to provide initial proof of concept in patients for use of this sequential BRAFi-HDACi therapy as the treatment of choice for the some 40,000 BRAF mutant melanomas that are diagnosed in the EU annually.

SummaryThis project aims to optimize and validate a promising therapeutic tool for combined cancer therapy, 2shRNA, in an ex vivo model system.
Combined therapies are of great significance nowadays, due to their key role in fighting, for instances, resistance processes during cancer treatment. Nonetheless, the drug combinations approved to date face several problems, such as cooperative toxicity effects, lack of efficiency and poor bioavailability. We have designed and synthesized 2shRNA, a new bifunctional RNA tool that can simultaneously attack two therapeutic targets involved in drug resistance pathways, and that can additionally bind other molecules such as peptide carriers or fluorophores, to improve delivery and efficacy. The 2shRNA nanostructure displayed low toxicity and excellent anti-proliferative properties in resistant HER2+ breast cancer cell lines. The present proposal is aimed at optimizing and validating this novel and promising RNA tool by combining state-of-the-art bioinformatics design and cycles of chemical refinement with biological evaluation in PDx-derived primary cell cultures and biodistribution studies in PDx mouse models. The proposed strategy presents a novel therapeutic approach with great potential to circumvent drug resistance in breast cancer, which is a major health challenge for our society. The ability of our biostable RNA tool to administer two drugs in a single dose could improve the quality of life of the patients, as fewer doses might be needed to stall disease progression.

This project aims to optimize and validate a promising therapeutic tool for combined cancer therapy, 2shRNA, in an ex vivo model system.
Combined therapies are of great significance nowadays, due to their key role in fighting, for instances, resistance processes during cancer treatment. Nonetheless, the drug combinations approved to date face several problems, such as cooperative toxicity effects, lack of efficiency and poor bioavailability. We have designed and synthesized 2shRNA, a new bifunctional RNA tool that can simultaneously attack two therapeutic targets involved in drug resistance pathways, and that can additionally bind other molecules such as peptide carriers or fluorophores, to improve delivery and efficacy. The 2shRNA nanostructure displayed low toxicity and excellent anti-proliferative properties in resistant HER2+ breast cancer cell lines. The present proposal is aimed at optimizing and validating this novel and promising RNA tool by combining state-of-the-art bioinformatics design and cycles of chemical refinement with biological evaluation in PDx-derived primary cell cultures and biodistribution studies in PDx mouse models. The proposed strategy presents a novel therapeutic approach with great potential to circumvent drug resistance in breast cancer, which is a major health challenge for our society. The ability of our biostable RNA tool to administer two drugs in a single dose could improve the quality of life of the patients, as fewer doses might be needed to stall disease progression.

SummaryThis proposal relates to the Proof of Concept stage investigation of exciting new findings in the ERC Advanced Grant ‘IMPUNEP’ project relating to the study and use of plasma-based processes. These findings offer significant advantages for the creation of complex 3D ceramic and ceramic-metal products at relatively low cost in an environmentally friendly manner. The potential applications of this new technology are very wide-ranging, and include the creation of new products as diverse as healthcare devices, MEMS and aero/automotive parts. Before we properly and fully identify the most promising applications, we need to investigate key aspects of the performance of materials created by this new method. This aspect wasn’t envisaged in the original proposal and involves research into the mechanical properties (especially the strength and elastic modulus) of these 3D parts and their response to deformation and dynamic displacements, as well as their physical (including electrical) properties. These components will be highly resistant to attack by aggressive (e.g. acidic) media as well as highly tolerant to both low (cryogenic) and high (combustion) temperatures. The expected applications opened up by this new method to produce ceramic and ceramic-metal components of complex shape are extensive. Hence the need for this Proof of Concept study, which will focus on validating the process for 3D ceramic-metal and ceramic parts and evaluating the mechanical, chemical, electrical and physical attributes of the 3D shapes, and will explore their potential applications in this pre-demonstration phase.

This proposal relates to the Proof of Concept stage investigation of exciting new findings in the ERC Advanced Grant ‘IMPUNEP’ project relating to the study and use of plasma-based processes. These findings offer significant advantages for the creation of complex 3D ceramic and ceramic-metal products at relatively low cost in an environmentally friendly manner. The potential applications of this new technology are very wide-ranging, and include the creation of new products as diverse as healthcare devices, MEMS and aero/automotive parts. Before we properly and fully identify the most promising applications, we need to investigate key aspects of the performance of materials created by this new method. This aspect wasn’t envisaged in the original proposal and involves research into the mechanical properties (especially the strength and elastic modulus) of these 3D parts and their response to deformation and dynamic displacements, as well as their physical (including electrical) properties. These components will be highly resistant to attack by aggressive (e.g. acidic) media as well as highly tolerant to both low (cryogenic) and high (combustion) temperatures. The expected applications opened up by this new method to produce ceramic and ceramic-metal components of complex shape are extensive. Hence the need for this Proof of Concept study, which will focus on validating the process for 3D ceramic-metal and ceramic parts and evaluating the mechanical, chemical, electrical and physical attributes of the 3D shapes, and will explore their potential applications in this pre-demonstration phase.

Max ERC Funding

149 500 €

Duration

Start date: 2019-01-01, End date: 2020-03-31

Project acronym3D-COUNT

Project3D-Integrated single photon detector

Researcher (PI)Fabio SCIARRINO

Host Institution (HI)UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA

Call DetailsProof of Concept (PoC), PC1, ERC-2015-PoC

SummaryPhotonics, in recognition of its strategic significance and pervasiveness throughout many industrial sectors, has been identified as one of the Key Enabling Technologies for Europe. Photonics in combination with quantum information science has great potential to facilitate, transform and innovate future technologies for the better. The Proof of Concept (PoC) project intends to contribute to this by developing and testing a communication platform prototype, comprised of single photon detectors, which are efficiently coupled to single mode fibers using an innovative laser written device. This enables the integration of single photon detectors on innovative glass waveguides. These glass integrated photonic circuits offer excellent specifics for on-chip quantum optics implementations in terms of scattering losses, offering flexibility of the waveguide geometry and ensuring high coupling efficiency with optical fibers.
The device developed and tested in the PoC, directly addresses a market need for an integrated and efficient on-chip communication systems. Current available systems have limitations involving high costs, complex production, and inefficient coupling of detectors to optical fibers. The proposed platform will offer 1.) a simplified production process, 2.) high optical fiber coupling efficiency 3.) improved performance levels, 4.) high cost efficiency, and 5.) compactness. Such systems can be applied in a wide range of communication and non-communication applications, such as free-space optical communication, quantum communication, quantum cryptography, DNA sequencing, single molecule detection and material analysis. Moreover, the future commercialisation of quantum computing is expected to create a vast demand for these communication systems.
In addition to the technology PoC, the project carries out IPR strategy considerations through patenting actions, determines the market potential, seeks market feedback, and plans for post-PoC commercialisation paths.

Photonics, in recognition of its strategic significance and pervasiveness throughout many industrial sectors, has been identified as one of the Key Enabling Technologies for Europe. Photonics in combination with quantum information science has great potential to facilitate, transform and innovate future technologies for the better. The Proof of Concept (PoC) project intends to contribute to this by developing and testing a communication platform prototype, comprised of single photon detectors, which are efficiently coupled to single mode fibers using an innovative laser written device. This enables the integration of single photon detectors on innovative glass waveguides. These glass integrated photonic circuits offer excellent specifics for on-chip quantum optics implementations in terms of scattering losses, offering flexibility of the waveguide geometry and ensuring high coupling efficiency with optical fibers.
The device developed and tested in the PoC, directly addresses a market need for an integrated and efficient on-chip communication systems. Current available systems have limitations involving high costs, complex production, and inefficient coupling of detectors to optical fibers. The proposed platform will offer 1.) a simplified production process, 2.) high optical fiber coupling efficiency 3.) improved performance levels, 4.) high cost efficiency, and 5.) compactness. Such systems can be applied in a wide range of communication and non-communication applications, such as free-space optical communication, quantum communication, quantum cryptography, DNA sequencing, single molecule detection and material analysis. Moreover, the future commercialisation of quantum computing is expected to create a vast demand for these communication systems.
In addition to the technology PoC, the project carries out IPR strategy considerations through patenting actions, determines the market potential, seeks market feedback, and plans for post-PoC commercialisation paths.

Max ERC Funding

150 000 €

Duration

Start date: 2016-02-01, End date: 2017-07-31

Project acronym3Dmaterials4Energy

ProjectHierarchical Inorganic Nanomaterials as Next Generation Catalysts and Filters

Researcher (PI)Taleb Mokari

Host Institution (HI)BEN-GURION UNIVERSITY OF THE NEGEV

Call DetailsProof of Concept (PoC), PC1, ERC-2016-PoC

SummaryIn the coming few decades, two major global grand challenges will continue to attract the attention of scientists and engineers in academia and industry: achieving clean water and clean energy. This PoC establishes the development of two prototypes, water oxidation catalyst and water purification filter, by creating inexpensive, abundant and versatile hierarchical structures of inorganic nanomaterials (HSINs).
The formation of HSINs has been one of the major obstacles toward achieving a technological progress in various applications. Presently, fabrication of well-defined 3-D structures can be achieved either by photo/electro lithography, assembly, 3D printing or template-mediated methods. Various structures with high quality/yield can be obtained through those techniques, however, these methods suffer from high cost, difficulty of fabrication of free-standing structures, and sometime the throughput is limited. On the other hand, the templated approaches usually are facile, low cost and offer several and complex structures in particular the ones obtained from nature.
Our invention is based on forming the HSINs using fossil templates from nature. We propose to harness the naturally designed morphologies of the fossil templates to rationally form hierarchical structures of nanomaterials. These structures have many advantageous, compared to the current state-of-the-art catalyst and filter, for example high surface area, high porosity, confined space (nano-reactor) and divers functionalities obtained by controlling the chemical composition of the inorganic material shell. Since these properties are important for achieving high performance, we propose HSINs as next generation water oxidation electrocatalyst and water purification filter.

In the coming few decades, two major global grand challenges will continue to attract the attention of scientists and engineers in academia and industry: achieving clean water and clean energy. This PoC establishes the development of two prototypes, water oxidation catalyst and water purification filter, by creating inexpensive, abundant and versatile hierarchical structures of inorganic nanomaterials (HSINs).
The formation of HSINs has been one of the major obstacles toward achieving a technological progress in various applications. Presently, fabrication of well-defined 3-D structures can be achieved either by photo/electro lithography, assembly, 3D printing or template-mediated methods. Various structures with high quality/yield can be obtained through those techniques, however, these methods suffer from high cost, difficulty of fabrication of free-standing structures, and sometime the throughput is limited. On the other hand, the templated approaches usually are facile, low cost and offer several and complex structures in particular the ones obtained from nature.
Our invention is based on forming the HSINs using fossil templates from nature. We propose to harness the naturally designed morphologies of the fossil templates to rationally form hierarchical structures of nanomaterials. These structures have many advantageous, compared to the current state-of-the-art catalyst and filter, for example high surface area, high porosity, confined space (nano-reactor) and divers functionalities obtained by controlling the chemical composition of the inorganic material shell. Since these properties are important for achieving high performance, we propose HSINs as next generation water oxidation electrocatalyst and water purification filter.

SummarySensors are ubiquitous in the modern technological world. From the numerous sensors everyone carries within their smartphone, through the pervasive nature of sensors within human machines, to the oncoming explosion of the “Internet of Things” promising immense interconnected networks of sensor enabled systems in virtually every aspect of human life. Micro-electro-mechanical systems (MEMS) as silicon integrated circuits (ICs) are the base technology for nearly all such sensors. In 2017 the worldwide market for MEMS sensors was valued at 10.3€ Billion up from 8.5€ Billion in 2016. It is forecast to grow to 48.4€ Billion in 2024. The use of MEMS ICs provides large-scale manufacture of very cheap sensors. However, there are also many disadvantages. They do not easily provide for rapid and localised/distributed manufacture and implementation. Prototyping requires multi-user foundry platforms or the availability of local facilities, both of which can be relatively expensive, and time consuming, for short runs of prototypes. There are also limitations to what can be achieved. For example, it is very difficult and expensive to make 3D MEMS silicon structures, and there are many issues with liquid interfacing of such systems.
3D printing to make relatively small structures is not new, and various groups have recently reported functionalized polymers. This project will produce 3D printed transducers using 3D printing techniques from the SASATIN ERC project. The 3D printing arrangement does not rely on specific materials purchased from the printer manufacturer.

Sensors are ubiquitous in the modern technological world. From the numerous sensors everyone carries within their smartphone, through the pervasive nature of sensors within human machines, to the oncoming explosion of the “Internet of Things” promising immense interconnected networks of sensor enabled systems in virtually every aspect of human life. Micro-electro-mechanical systems (MEMS) as silicon integrated circuits (ICs) are the base technology for nearly all such sensors. In 2017 the worldwide market for MEMS sensors was valued at 10.3€ Billion up from 8.5€ Billion in 2016. It is forecast to grow to 48.4€ Billion in 2024. The use of MEMS ICs provides large-scale manufacture of very cheap sensors. However, there are also many disadvantages. They do not easily provide for rapid and localised/distributed manufacture and implementation. Prototyping requires multi-user foundry platforms or the availability of local facilities, both of which can be relatively expensive, and time consuming, for short runs of prototypes. There are also limitations to what can be achieved. For example, it is very difficult and expensive to make 3D MEMS silicon structures, and there are many issues with liquid interfacing of such systems.
3D printing to make relatively small structures is not new, and various groups have recently reported functionalized polymers. This project will produce 3D printed transducers using 3D printing techniques from the SASATIN ERC project. The 3D printing arrangement does not rely on specific materials purchased from the printer manufacturer.

Max ERC Funding

146 334 €

Duration

Start date: 2018-07-01, End date: 2019-12-31

Project acronym3DV

ProjectSensor for 3D Vision

Researcher (PI)Alberto BROGGI

Host Institution (HI)UNIVERSITA DEGLI STUDI DI PARMA

Call DetailsProof of Concept (PoC), PC1, ERC-2011-PoC

Summary"A low-cost sensor able to perceive 3D information would be a breakthrough for a number of applications. Automotive applications would benefit from a low-cost obstacle detector to increase road safety; agricultural vehicles would be able to sense the environment and perform precise (and even autonomous) maneuvers improving their effectiveness; efficient sensing would be a key also to future building automation: elevators doors would close just after boarding and keep open when detecting people's intention to enter, automatic doors would not open when individuals would move in their sensed area but without the intention to cross the door. Even the entertainment industry, which lately invested massively on innovative and interactive sensors, would benefit from precise 3D sensors working even outdoor or in combination with multiple identical sensors.
This proposal is aimed at preparing an engineered version of the current stereo-based system developed for vehicles within the OFAV ERC-funded Advanced Grant and currently under test in many other application domains. It is based on two microcameras and a smart software reconstructing the 3D environment; the software will be ported on a low-cost FPGA+DSP integrated into the sensor box, providing a small and light passive sensor for a variety of applications that nowadays either use other technologies (laser based) or are not able to reach the performance provided by this sensor (e.g. IR-based elevators' door control which is not working in highly illuminated sites and covers only smaller areas).
The algorithm which is now working on a PC-based platform is owned by the team working for the OFAV Project and delivers superb results in terms of accuracy. This proposal is intended to provide resources to implement this solution in hardware and produce a low-cost, small-sized, and high performance sensor to be used in a very wide range of applications."

"A low-cost sensor able to perceive 3D information would be a breakthrough for a number of applications. Automotive applications would benefit from a low-cost obstacle detector to increase road safety; agricultural vehicles would be able to sense the environment and perform precise (and even autonomous) maneuvers improving their effectiveness; efficient sensing would be a key also to future building automation: elevators doors would close just after boarding and keep open when detecting people's intention to enter, automatic doors would not open when individuals would move in their sensed area but without the intention to cross the door. Even the entertainment industry, which lately invested massively on innovative and interactive sensors, would benefit from precise 3D sensors working even outdoor or in combination with multiple identical sensors.
This proposal is aimed at preparing an engineered version of the current stereo-based system developed for vehicles within the OFAV ERC-funded Advanced Grant and currently under test in many other application domains. It is based on two microcameras and a smart software reconstructing the 3D environment; the software will be ported on a low-cost FPGA+DSP integrated into the sensor box, providing a small and light passive sensor for a variety of applications that nowadays either use other technologies (laser based) or are not able to reach the performance provided by this sensor (e.g. IR-based elevators' door control which is not working in highly illuminated sites and covers only smaller areas).
The algorithm which is now working on a PC-based platform is owned by the team working for the OFAV Project and delivers superb results in terms of accuracy. This proposal is intended to provide resources to implement this solution in hardware and produce a low-cost, small-sized, and high performance sensor to be used in a very wide range of applications."

Max ERC Funding

148 061 €

Duration

Start date: 2012-06-01, End date: 2013-10-31

Project acronym7TReImHo

Project7kDa TSLP as a novel type of anti-inflammatory agent to re-establish immune homeostasis

Researcher (PI)Maria RESCIGNO

Host Institution (HI)ISTITUTO EUROPEO DI ONCOLOGIA SRL

Call DetailsProof of Concept (PoC), PC1, ERC-2012-PoC

SummaryIntestinal homeostasis is a complex event that relies on different interactions between the host and the commensal flora, also called microbiota. The microbiota is a source of gene products that are required for several functions linked to digestion and energy harvest, thus it has to be tolerated, but at the same time controlled. We have shown that the capacity to tolerate the microbiota is linked to a close interaction between epithelial cells, that are the first line of defence against luminal microorganisms, and specialized immune cells called dendritic cells, that acquire a tolerogenic phenotype and drive the development of T regulatory cells, capable to control the development of inflammatory responses to bacteria. We have identified several effectors mediating this control and focused on a cytokine called thymic stromal lymphopoietin (TSLP) that is released constitutively by epithelial cells and is strongly downregulated in inflammatory bowel disease (IBD). By contrast, in other inflammatory disorders like allergy or asthma, TSLP has been shown to be upregulated and to mediate disease.
This apparent controversy is solved when considering that TSLP comes in two different isoforms: a short (sTSLP) and a long (lTSLP). sTSLP has been completely neglected in the literature as most of the reagents do not distinguish it from lTSLP. Within the ERC project Dendroworld, we have generated all the tools to study the function of these two isoforms. We discovered that in IBD there is an inverse correlation between sTSLP and lTSLP. lTSLP is drastically upregulated by recruited immune cells, while sTSLP is downregulated in epithelial cells. Hence, we hypothesized and confirmed that the two isoforms had different activities, with the sTSLP being anti-inflammatory and lTSLP being inflammatory.
In this POC we propose scientific and commercialization activities to bring sTSLP to the market as a new class of anti-inflammatory drugs capable of re-establishing immune homeostasis.

Intestinal homeostasis is a complex event that relies on different interactions between the host and the commensal flora, also called microbiota. The microbiota is a source of gene products that are required for several functions linked to digestion and energy harvest, thus it has to be tolerated, but at the same time controlled. We have shown that the capacity to tolerate the microbiota is linked to a close interaction between epithelial cells, that are the first line of defence against luminal microorganisms, and specialized immune cells called dendritic cells, that acquire a tolerogenic phenotype and drive the development of T regulatory cells, capable to control the development of inflammatory responses to bacteria. We have identified several effectors mediating this control and focused on a cytokine called thymic stromal lymphopoietin (TSLP) that is released constitutively by epithelial cells and is strongly downregulated in inflammatory bowel disease (IBD). By contrast, in other inflammatory disorders like allergy or asthma, TSLP has been shown to be upregulated and to mediate disease.
This apparent controversy is solved when considering that TSLP comes in two different isoforms: a short (sTSLP) and a long (lTSLP). sTSLP has been completely neglected in the literature as most of the reagents do not distinguish it from lTSLP. Within the ERC project Dendroworld, we have generated all the tools to study the function of these two isoforms. We discovered that in IBD there is an inverse correlation between sTSLP and lTSLP. lTSLP is drastically upregulated by recruited immune cells, while sTSLP is downregulated in epithelial cells. Hence, we hypothesized and confirmed that the two isoforms had different activities, with the sTSLP being anti-inflammatory and lTSLP being inflammatory.
In this POC we propose scientific and commercialization activities to bring sTSLP to the market as a new class of anti-inflammatory drugs capable of re-establishing immune homeostasis.

Max ERC Funding

146 917 €

Duration

Start date: 2013-07-01, End date: 2014-06-30

Project acronymA CACTUS

ProjectAntibody-free method for Counting All Circulating TUmour cellS while maintaining them alive and intact

Researcher (PI)Giacinto Scoles

Host Institution (HI)UNIVERSITA DEGLI STUDI DI UDINE

Call DetailsProof of Concept (PoC), PC1, ERC-2014-PoC

SummaryThe problem: Cancer metastases are responsible for 90% of cancer-associated deaths. Circulating tumour cells (CTCs) that enter the blood stream on their way to potential metastatic sites are of obvious interest to evaluate correctly patient treatment and therefore influence outcome. CTCs have been identified in bladder, gastric, prostate, lung, breast and colon cancer. The only FDA approved CTCs detection system is Veridex’ CellSearch, which detects only epithelial cancer cells using antibody labelling. Recent evidence showed that non-epithelial cancer cells, which are not detected by CellSearch, are of critical importance in cancer progression.
The idea: Our CTC detection method is based, instead of on antibody labelling, on metabolic features of cancer cells, thus providing potential for detecting both epithelial and mesenchymal cancer cells. Cancer cells induce environmental changes; e.g. in aerobic conditions most cancer cells display a high rate of glycolysis with lactate production in the cytosol, known as the Warburg effect. By separating cells into micro-droplets of pico-liter volume using micro-fluidic water-in-oil emulsions and by characterising the microenvironment surrounding them, CTCs are detected by probing for environmental changes using pH sensitive dyes or enzymatic lactate assays. Our inexpensive diagnostic method provides a way to count and isolate CTCs without any labelling while maintaining cells alive and intact for further studies.
The project: “A CACTUS” is meant to assess the feasibility of commercialising the developed method for counting and sorting CTCs and develop a proper commercialisation strategy. The final goal of this project is to develop a proposition package consisting of technical proof of concept, the business proposition and strategy and an IP portfolio and strategy. This information will be presented in an attractive business plan that will be proposed to potential investors.

The problem: Cancer metastases are responsible for 90% of cancer-associated deaths. Circulating tumour cells (CTCs) that enter the blood stream on their way to potential metastatic sites are of obvious interest to evaluate correctly patient treatment and therefore influence outcome. CTCs have been identified in bladder, gastric, prostate, lung, breast and colon cancer. The only FDA approved CTCs detection system is Veridex’ CellSearch, which detects only epithelial cancer cells using antibody labelling. Recent evidence showed that non-epithelial cancer cells, which are not detected by CellSearch, are of critical importance in cancer progression.
The idea: Our CTC detection method is based, instead of on antibody labelling, on metabolic features of cancer cells, thus providing potential for detecting both epithelial and mesenchymal cancer cells. Cancer cells induce environmental changes; e.g. in aerobic conditions most cancer cells display a high rate of glycolysis with lactate production in the cytosol, known as the Warburg effect. By separating cells into micro-droplets of pico-liter volume using micro-fluidic water-in-oil emulsions and by characterising the microenvironment surrounding them, CTCs are detected by probing for environmental changes using pH sensitive dyes or enzymatic lactate assays. Our inexpensive diagnostic method provides a way to count and isolate CTCs without any labelling while maintaining cells alive and intact for further studies.
The project: “A CACTUS” is meant to assess the feasibility of commercialising the developed method for counting and sorting CTCs and develop a proper commercialisation strategy. The final goal of this project is to develop a proposition package consisting of technical proof of concept, the business proposition and strategy and an IP portfolio and strategy. This information will be presented in an attractive business plan that will be proposed to potential investors.

Max ERC Funding

149 875 €

Duration

Start date: 2015-04-01, End date: 2016-09-30

Project acronymAB-SWITCH

ProjectEvaluation of commercial potential of a low-cost kit based on DNA-nanoswitches for the single-step measurement of diagnostic antibodies

Researcher (PI)Francesco RICCI

Host Institution (HI)UNIVERSITA DEGLI STUDI DI ROMA TOR VERGATA

Call DetailsProof of Concept (PoC), ERC-2016-PoC, ERC-2016-PoC

Summary"Antibodies are among the most widely monitored class of diagnostic biomarkers. Immunoassays market now covers about 1/3 of the global market of in-vitro diagnostics (about $50 billion). However, current methods for the detection of diagnostic antibodies are either qualitative or require cumbersome, resource-intensive laboratory procedures that need hours to provide clinicians with diagnostic information. A new method for fast and low-cost detection of antibodies will have a strong economic impact in the market of in-vitro diagnostics and Immunoassays.
During our ERC Starting Grant project ""Nature Nanodevices"" we have developed a novel diagnostic technology for the detection of clinically relevant antibodies in serum and other body fluids. The platform (here named Ab-switch) supports the fluorescent detection of diagnostic antibodies (for example, HIV diagnostic antibodies) in a rapid (<3 minutes), single-step and low-cost fashion.
The goal of this Proof of Concept project is to bring our promising platform to the proof of diagnostic market and exploit its innovative features for commercial purposes. We will focus our initial efforts in the development of rapid kits for the detection of antibodies diagnostic of HIV. We will 1) Fully characterize the Ab-switch product in terms of analytical performances (i.e. sensitivity, specificity, stability etc.) with direct comparison with other commercial kits; 2) Prepare a Manufacturing Plan for producing/testing the Ab-switch; 3) Establish an IP strategy for patent filing and maintenance; 4) Determine a business and commercialization planning."

"Antibodies are among the most widely monitored class of diagnostic biomarkers. Immunoassays market now covers about 1/3 of the global market of in-vitro diagnostics (about $50 billion). However, current methods for the detection of diagnostic antibodies are either qualitative or require cumbersome, resource-intensive laboratory procedures that need hours to provide clinicians with diagnostic information. A new method for fast and low-cost detection of antibodies will have a strong economic impact in the market of in-vitro diagnostics and Immunoassays.
During our ERC Starting Grant project ""Nature Nanodevices"" we have developed a novel diagnostic technology for the detection of clinically relevant antibodies in serum and other body fluids. The platform (here named Ab-switch) supports the fluorescent detection of diagnostic antibodies (for example, HIV diagnostic antibodies) in a rapid (<3 minutes), single-step and low-cost fashion.
The goal of this Proof of Concept project is to bring our promising platform to the proof of diagnostic market and exploit its innovative features for commercial purposes. We will focus our initial efforts in the development of rapid kits for the detection of antibodies diagnostic of HIV. We will 1) Fully characterize the Ab-switch product in terms of analytical performances (i.e. sensitivity, specificity, stability etc.) with direct comparison with other commercial kits; 2) Prepare a Manufacturing Plan for producing/testing the Ab-switch; 3) Establish an IP strategy for patent filing and maintenance; 4) Determine a business and commercialization planning."

Max ERC Funding

150 000 €

Duration

Start date: 2017-02-01, End date: 2018-07-31

Project acronymAbCURE_COPD

ProjectAntibody mediated clearance of senescent cells for treatment of COPD

Researcher (PI)Valery KRIZHANOVSKY

Host Institution (HI)WEIZMANN INSTITUTE OF SCIENCE

Call DetailsProof of Concept (PoC), ERC-2017-PoC

SummaryChronic Obstructive Pulmonary Disease (COPD) is a group of chronic diseases characterized by airflow limitations in the lung. COPD is a critical international health problem. It is estimated to affect up to 600 million people worldwide and by 2020 it will become the third most frequent cause of death. In Europe alone, COPD affects up to 10% of people (i.e. more people than breast cancer and diabetes) and it takes the life of around 300,000 Europeans each year. Up to date, COPD has no cure as current treatments fail to halt the long-term decline in lung function. They are only able to delay its progression. Those treatments however, are associated with a variety of side effects some of which can be acute and even life threatening. Thus, COPD remains a disease with a significant unmet medical need.
In this project (acronymed AbCURE_COPD) we intend to carry out a set of necessary activities for the evaluation of a potentially groundbreaking approach for treating COPD. Our approach is focusing on antibody-mediated clearance of senescent cells which accumulate in tissues with age and contribute to multiple age-related diseases, including COPD. The goal of the PoC project is two-fold. (1) The first goal is to establish the technical feasibility of our idea by testing the effect of senescence-specific antibodies on COPD development and progression by implementing COPD mouse model we developed. (2) The second goal is to establish the business feasibility of our revolutionary approach by taking the necessary steps towards its commercialization, focusing on the creation of strategic alliances with key private sector companies. We firmly believe that with our approach we can significantly extend the health span and improve the quality of life of COPD patients. Equally important, our approach will pave the way for the development of novel treatment strategies applicable to other age-related diseases, such as osteoarthritis, cardiovascular, and neurodegenerative diseases.

Chronic Obstructive Pulmonary Disease (COPD) is a group of chronic diseases characterized by airflow limitations in the lung. COPD is a critical international health problem. It is estimated to affect up to 600 million people worldwide and by 2020 it will become the third most frequent cause of death. In Europe alone, COPD affects up to 10% of people (i.e. more people than breast cancer and diabetes) and it takes the life of around 300,000 Europeans each year. Up to date, COPD has no cure as current treatments fail to halt the long-term decline in lung function. They are only able to delay its progression. Those treatments however, are associated with a variety of side effects some of which can be acute and even life threatening. Thus, COPD remains a disease with a significant unmet medical need.
In this project (acronymed AbCURE_COPD) we intend to carry out a set of necessary activities for the evaluation of a potentially groundbreaking approach for treating COPD. Our approach is focusing on antibody-mediated clearance of senescent cells which accumulate in tissues with age and contribute to multiple age-related diseases, including COPD. The goal of the PoC project is two-fold. (1) The first goal is to establish the technical feasibility of our idea by testing the effect of senescence-specific antibodies on COPD development and progression by implementing COPD mouse model we developed. (2) The second goal is to establish the business feasibility of our revolutionary approach by taking the necessary steps towards its commercialization, focusing on the creation of strategic alliances with key private sector companies. We firmly believe that with our approach we can significantly extend the health span and improve the quality of life of COPD patients. Equally important, our approach will pave the way for the development of novel treatment strategies applicable to other age-related diseases, such as osteoarthritis, cardiovascular, and neurodegenerative diseases.

SummaryAntibody detection assays are used in many fields of biomedicine including the diagnosis of infectious diseases, autoimmune diseases and allergies. Current analytical techniques for antibody detection come with intrinsic limitations such as the requirement for multiple time-consuming incubation steps, multiple reagents, and/or sophisticated equipment. Supported by an ERC consolidator grant we have developed a highly modular sensor concept for antibody-responsive reporter enzymes (AbSens) that addresses many of these challenges. Key advantages include the ability to monitor antibodies directly in solution, easy read-out based on a simple color reaction, adaptability to target any antibody of interest, and high affinity and specificity. We believe that this generic sensor platform could find applications in low-cost point-of-care diagnostics, clinical research, and the development of therapeutic antibodies.
The goal of AbSens is to identify those opportunities in the huge market of antibody-based diagnostics where our sensor platform provides unique advantages over existing technologies, both in terms of analytical performance and economics.
To enable the next step towards commercialization, the analytical performance of our technology will be compared to current gold standards using relevant clinical samples in collaboration with commercial parties and clinicians. Other commercially important parameters are the long-term stability of the assay components and the development of a yeast-based production system to lower the cost of enzyme production. Based on an in-depth market analysis and the feedback we receive from external stakeholders on the performance of our technology, a realistic strategy will be developed for the further commercialization. In anticipation of exploring the commercialization of our AbSens technology we filed a US provisional patent application in Sept. 2012 on the key underlying technology, which was recently continued via the PCT route.

Antibody detection assays are used in many fields of biomedicine including the diagnosis of infectious diseases, autoimmune diseases and allergies. Current analytical techniques for antibody detection come with intrinsic limitations such as the requirement for multiple time-consuming incubation steps, multiple reagents, and/or sophisticated equipment. Supported by an ERC consolidator grant we have developed a highly modular sensor concept for antibody-responsive reporter enzymes (AbSens) that addresses many of these challenges. Key advantages include the ability to monitor antibodies directly in solution, easy read-out based on a simple color reaction, adaptability to target any antibody of interest, and high affinity and specificity. We believe that this generic sensor platform could find applications in low-cost point-of-care diagnostics, clinical research, and the development of therapeutic antibodies.
The goal of AbSens is to identify those opportunities in the huge market of antibody-based diagnostics where our sensor platform provides unique advantages over existing technologies, both in terms of analytical performance and economics.
To enable the next step towards commercialization, the analytical performance of our technology will be compared to current gold standards using relevant clinical samples in collaboration with commercial parties and clinicians. Other commercially important parameters are the long-term stability of the assay components and the development of a yeast-based production system to lower the cost of enzyme production. Based on an in-depth market analysis and the feedback we receive from external stakeholders on the performance of our technology, a realistic strategy will be developed for the further commercialization. In anticipation of exploring the commercialization of our AbSens technology we filed a US provisional patent application in Sept. 2012 on the key underlying technology, which was recently continued via the PCT route.

Max ERC Funding

150 000 €

Duration

Start date: 2014-09-01, End date: 2015-08-31

Project acronymACAP

ProjectAsset Centric Adaptive Protection

Researcher (PI)Bashar NUSEIBEH

Host Institution (HI)UNIVERSITY OF LIMERICK

Call DetailsProof of Concept (PoC), PC1, ERC-2015-PoC

SummaryThe proliferation of mobile and ubiquitous computing technology is radically changing the ways in which we live our lives: from interacting with friends & family, to how we produce & consume services and engage in business. However, this pervasiveness of technologies, and their increasingly seamless integration and inter-operation, are blurring the boundaries between systems. This poses significant challenges for security engineers who aim to design systems that monitor and control the movement of digital or physical assets across those boundaries.
My ERC Advanced Grant on Adaptive Security and Privacy (ASAP) is investigating ways in which security controls can change in response to changes in the context of operation of systems. However, since the monitoring of such elusive and changing boundaries is difficult, we have developed an adaptive security approach that monitors valuable assets that are managed by a system, and changes the means and extent by which those assets are protected in response to changes in assets and their values. This could radically change the way security is designed and implemented in a range of applications because it allows for a choice of appropriate protection, depending on particular requirements.
In ASAP, we developed the modelling and computational capabilities of our approach, including some prototype tool fragments that demonstrate the approach in our lab. However, interest from our industrial collaborators, evidenced by direct funding of follow-on research, and the demonstration of our prototypes to senior management and potential customers, has motivated us to pursue a proof of concept (PoC) assessment of our work in a more systematic and targeted way. To this end, this ERC PoC will:
1) Develop a robust prototype demonstrator, instantiated in two application areas (access control & cloud computing);
2) Conduct a market analysis, aided by the demonstrator;
3) Subject to (2), develop a commercialisation strategy and plan

The proliferation of mobile and ubiquitous computing technology is radically changing the ways in which we live our lives: from interacting with friends & family, to how we produce & consume services and engage in business. However, this pervasiveness of technologies, and their increasingly seamless integration and inter-operation, are blurring the boundaries between systems. This poses significant challenges for security engineers who aim to design systems that monitor and control the movement of digital or physical assets across those boundaries.
My ERC Advanced Grant on Adaptive Security and Privacy (ASAP) is investigating ways in which security controls can change in response to changes in the context of operation of systems. However, since the monitoring of such elusive and changing boundaries is difficult, we have developed an adaptive security approach that monitors valuable assets that are managed by a system, and changes the means and extent by which those assets are protected in response to changes in assets and their values. This could radically change the way security is designed and implemented in a range of applications because it allows for a choice of appropriate protection, depending on particular requirements.
In ASAP, we developed the modelling and computational capabilities of our approach, including some prototype tool fragments that demonstrate the approach in our lab. However, interest from our industrial collaborators, evidenced by direct funding of follow-on research, and the demonstration of our prototypes to senior management and potential customers, has motivated us to pursue a proof of concept (PoC) assessment of our work in a more systematic and targeted way. To this end, this ERC PoC will:
1) Develop a robust prototype demonstrator, instantiated in two application areas (access control & cloud computing);
2) Conduct a market analysis, aided by the demonstrator;
3) Subject to (2), develop a commercialisation strategy and plan

SummaryACOFORS has been designed with the ultimate goal of preparing commercialisation of Acoustic Force Spectroscopy (AFS). AFS is a completely new and powerful technique for determining biomolecular mechanics and structure of single molecules such as DNA and proteins. These studies are performed on a large scale by biologists and within pharmaceutical companies for e.g. drug discovery and development. Current technologies for force spectroscopy (FS) represent a $50+ million market, but are expensive, require high levels of specialism and are laborious. AFS, invented in the laboratory of Prof. Wuite, is much simpler to use, can be operated in high-throughput mode and can become available at relative low cost. As such, AFS vastly expands the possibilities of FS and makes it available to a much wider community. This makes AFS a very attractive technology for science and business, both from the perspective of the user and of the seller.
In ACOFORS, a team of scientists and business developers will transform the current prototype in a marketable product, strengthen the intellectual property position, build a solid business case based on an extensive market analysis and take steps towards licensing the technology to industry.

ACOFORS has been designed with the ultimate goal of preparing commercialisation of Acoustic Force Spectroscopy (AFS). AFS is a completely new and powerful technique for determining biomolecular mechanics and structure of single molecules such as DNA and proteins. These studies are performed on a large scale by biologists and within pharmaceutical companies for e.g. drug discovery and development. Current technologies for force spectroscopy (FS) represent a $50+ million market, but are expensive, require high levels of specialism and are laborious. AFS, invented in the laboratory of Prof. Wuite, is much simpler to use, can be operated in high-throughput mode and can become available at relative low cost. As such, AFS vastly expands the possibilities of FS and makes it available to a much wider community. This makes AFS a very attractive technology for science and business, both from the perspective of the user and of the seller.
In ACOFORS, a team of scientists and business developers will transform the current prototype in a marketable product, strengthen the intellectual property position, build a solid business case based on an extensive market analysis and take steps towards licensing the technology to industry.

Max ERC Funding

150 000 €

Duration

Start date: 2015-07-01, End date: 2016-06-30

Project acronymACOM

ProjectCommercial feasibility of microbial therapy

Researcher (PI)Willem Meindert DE VOS

Host Institution (HI)WAGENINGEN UNIVERSITY

Call DetailsProof of Concept (PoC), PC1, ERC-2013-PoC

SummaryOur body is colonized by complex microbial communities (our microbiome) that are most abundant in the intestinal tract where they contribute significantly to our health and disease. It has been established that aberrations in our microbiome are of particular importance in obesity, type 2 diabetes and metabolic syndrome, rapidly growing diseases with a drug market volume of over 5 B$ per year. We have discovered in the ERC project Microbes Inside that a particular bacterium is able to modify the intestinal microbiome and may be used to develop a new approach to treat these and other metabolic diseases. The Proof of Concept project ACOM aims to confirm the commercial and technological feasibility of this approach, consolidate and expand our IP position, and develop a product development plan. These form the elements of a business plan that is expected to result in establishing a spin out company (ACOM).

Our body is colonized by complex microbial communities (our microbiome) that are most abundant in the intestinal tract where they contribute significantly to our health and disease. It has been established that aberrations in our microbiome are of particular importance in obesity, type 2 diabetes and metabolic syndrome, rapidly growing diseases with a drug market volume of over 5 B$ per year. We have discovered in the ERC project Microbes Inside that a particular bacterium is able to modify the intestinal microbiome and may be used to develop a new approach to treat these and other metabolic diseases. The Proof of Concept project ACOM aims to confirm the commercial and technological feasibility of this approach, consolidate and expand our IP position, and develop a product development plan. These form the elements of a business plan that is expected to result in establishing a spin out company (ACOM).

Max ERC Funding

142 000 €

Duration

Start date: 2014-06-01, End date: 2015-05-31

Project acronymACOUSEQ

ProjectAcoustics for Next Generation Sequencing

Researcher (PI)Jonathan Mark Cooper

Host Institution (HI)UNIVERSITY OF GLASGOW

Call DetailsProof of Concept (PoC), PC1, ERC-2016-PoC

SummarySince completion of the first human genome sequence, the demand for cheaper and faster sequencing methods has increased enormously. This need has driven the development of second-generation sequencing methods, or next-generation sequencing (also known as NGS or high throughput sequencing). The creation of these platforms has made sequencing accessible to more laboratories, rapidly increasing the volume of research, including clinical diagnostics and its use in directing treatment (precision medicine). The applications of NGS are also allowing rapid advances in clinically related fields such as public health and epidemiology. Such developments illustrate why sequencing is now the fastest-growing area in genomics (+23% p.a.). The activity is said to be worth $2.5B this year, and poised to reach ~$9B by 2020. In any workflow, prior to the sequencing reactions, a number of pre-sequencing steps are required, including the fragmentation of the DNA into smaller sizes for processing, size selection, library preparation and target enrichment. This proposal is specifically concerned with this latter area, namely DNA fragmentation – now widely acknowledged across the industry as being the most important technological bottleneck in the pre-sequencing workflow. Our new method for DNA fragmentation – involving using surface acoustic waves will enable sample preparation from lower sample volumes using lower powers. It also has the potential to allow the seamless integration of fragmentation into sequencing instrumentation, opening up the possibility of “sample to answer” diagnostics. In the near term this will enable the implementation of sample preparation pre-sequencing steps within the NGS instruments. In the longer term, our techniques will also enable us to develop methods for field-based DNA sequencing – as may be required for determining “microbial resistance” and informing the treatment of infectious disease in the face of the emergence of drug resistance.

Since completion of the first human genome sequence, the demand for cheaper and faster sequencing methods has increased enormously. This need has driven the development of second-generation sequencing methods, or next-generation sequencing (also known as NGS or high throughput sequencing). The creation of these platforms has made sequencing accessible to more laboratories, rapidly increasing the volume of research, including clinical diagnostics and its use in directing treatment (precision medicine). The applications of NGS are also allowing rapid advances in clinically related fields such as public health and epidemiology. Such developments illustrate why sequencing is now the fastest-growing area in genomics (+23% p.a.). The activity is said to be worth $2.5B this year, and poised to reach ~$9B by 2020. In any workflow, prior to the sequencing reactions, a number of pre-sequencing steps are required, including the fragmentation of the DNA into smaller sizes for processing, size selection, library preparation and target enrichment. This proposal is specifically concerned with this latter area, namely DNA fragmentation – now widely acknowledged across the industry as being the most important technological bottleneck in the pre-sequencing workflow. Our new method for DNA fragmentation – involving using surface acoustic waves will enable sample preparation from lower sample volumes using lower powers. It also has the potential to allow the seamless integration of fragmentation into sequencing instrumentation, opening up the possibility of “sample to answer” diagnostics. In the near term this will enable the implementation of sample preparation pre-sequencing steps within the NGS instruments. In the longer term, our techniques will also enable us to develop methods for field-based DNA sequencing – as may be required for determining “microbial resistance” and informing the treatment of infectious disease in the face of the emergence of drug resistance.

SummaryTumor Necrosis Factor (TNF) is a homotrimeric pro-inflammatory cytokine that was originally discovered based on its extraordinary antitumor activity. However, its shock-inducing properties, causing hypotension, leukopenia and multiple organ failure, prevented its systemic use in cancer treatment. With this proof-of-concept study we want to evaluate a novel class of cell-targeted TNFs with strongly reduced systemic toxicities (AcTafactors). In these engineered immuno-cytokines, single-chain TNFs that harbor mutations to reduce the affinity for its receptor(s) are fused to a cell- specific targeting domain. Whilst almost no biological activity is observed on non-targeted cells, thus preventing systemic toxicity, avidity effects at the targeted cell membrane lead to recovery of over 90% of the TNF signaling activity. In this project we propose a lead optimization program to further improve the lead AcTafactors identified in the context of the ERC Advanced Grant project and to evaluate the resulting molecules for their ability to target the tumor (neo)vasculature in clinically relevant murine tumor models. The pre-clinical proof-of-concept we aim for represents a first step towards clinical development and ultimately potential market approval of an effective AcTafactor anti-cancer therapy.

Tumor Necrosis Factor (TNF) is a homotrimeric pro-inflammatory cytokine that was originally discovered based on its extraordinary antitumor activity. However, its shock-inducing properties, causing hypotension, leukopenia and multiple organ failure, prevented its systemic use in cancer treatment. With this proof-of-concept study we want to evaluate a novel class of cell-targeted TNFs with strongly reduced systemic toxicities (AcTafactors). In these engineered immuno-cytokines, single-chain TNFs that harbor mutations to reduce the affinity for its receptor(s) are fused to a cell- specific targeting domain. Whilst almost no biological activity is observed on non-targeted cells, thus preventing systemic toxicity, avidity effects at the targeted cell membrane lead to recovery of over 90% of the TNF signaling activity. In this project we propose a lead optimization program to further improve the lead AcTafactors identified in the context of the ERC Advanced Grant project and to evaluate the resulting molecules for their ability to target the tumor (neo)vasculature in clinically relevant murine tumor models. The pre-clinical proof-of-concept we aim for represents a first step towards clinical development and ultimately potential market approval of an effective AcTafactor anti-cancer therapy.

Max ERC Funding

149 320 €

Duration

Start date: 2015-11-01, End date: 2017-04-30

Project acronymACTICELL

ProjectPrecision confiner for mechanical cell activation

Researcher (PI)Matthieu PIEL

Host Institution (HI)INSTITUT CURIE

Call DetailsProof of Concept (PoC), PC1, ERC-2016-PoC

SummaryIn tissues, cells have their physical space constrained by neighbouring cells and extracellular matrix. In the PROMICO ERC project, our team proposed to specifically address the effect of physical confinement on normal and cancer cells that are dividing and migrating, using new pathophysiologically relevant in vitro approaches based on innovative micro-fabrication techniques. One of the devices we developed was meant to quantitatively control two key parameters of the cell environment: its geometry and its surface chemical properties. The main technical breakthrough was achieved using micro-fabricated elastomeric structures bound to a hard substrate (Le Berre Integrative Biology, 2012). The method led to important fundamental discoveries in cell biology (Lancaster Dev Cell 2013, Le Berre PRL 2013, Liu Cell 2015, Raab Science 2016). In part based on our findings, the notion that confinement is a crucial parameter for cell physiology has spread through the cell biology. Based on this, our idea is that cell confinement could be used as a powerfull cell conditioning technology, to change the cell state and offer new opportunities for fundamental research in cell biology, but also in cell therapies and drug screening. However, our current method to confine cells is not adapted to large scale cell conditioning applications, because the throughput and reliability of the device is still too low and because the recovery of cells after confinement remain poorly controlled. It is thus now timely to develop a robust and versatile cell confiner adapted to use in any cell biology lab, in academy and in industry, with no prior experience in micro-fabrication. Achieving this goal involves a complete change of technology compared to the ‘homemade’ PDMS device we have been using so far. We will also perform proofs of concept of its use for its application in cell based therapies, such as cancer immunotherapy, by testing the possibility to mechanically activate dendritic cells.

In tissues, cells have their physical space constrained by neighbouring cells and extracellular matrix. In the PROMICO ERC project, our team proposed to specifically address the effect of physical confinement on normal and cancer cells that are dividing and migrating, using new pathophysiologically relevant in vitro approaches based on innovative micro-fabrication techniques. One of the devices we developed was meant to quantitatively control two key parameters of the cell environment: its geometry and its surface chemical properties. The main technical breakthrough was achieved using micro-fabricated elastomeric structures bound to a hard substrate (Le Berre Integrative Biology, 2012). The method led to important fundamental discoveries in cell biology (Lancaster Dev Cell 2013, Le Berre PRL 2013, Liu Cell 2015, Raab Science 2016). In part based on our findings, the notion that confinement is a crucial parameter for cell physiology has spread through the cell biology. Based on this, our idea is that cell confinement could be used as a powerfull cell conditioning technology, to change the cell state and offer new opportunities for fundamental research in cell biology, but also in cell therapies and drug screening. However, our current method to confine cells is not adapted to large scale cell conditioning applications, because the throughput and reliability of the device is still too low and because the recovery of cells after confinement remain poorly controlled. It is thus now timely to develop a robust and versatile cell confiner adapted to use in any cell biology lab, in academy and in industry, with no prior experience in micro-fabrication. Achieving this goal involves a complete change of technology compared to the ‘homemade’ PDMS device we have been using so far. We will also perform proofs of concept of its use for its application in cell based therapies, such as cancer immunotherapy, by testing the possibility to mechanically activate dendritic cells.

SummaryRobot-assisted and minimally invasive medical procedures are impacting medical care by increasing accuracy, reducing cost, and minimizing patient discomfort and recovery times after interventions. Developers of commercial robotic surgical systems and medical device manufacturers look for realistic phantoms that can be used in place of animal experiments or cadavers to test procedures and to train medical personnel. Existing phantoms are either made from hard materials, or they lack anatomical detail, and they are mainly passive and thus unrealistic.
Here, we use recently developed fabrication know-how and expertise within our ERC-funded research to develop the first active artificial urinary tract model that includes a kidney, a bladder, and a prostate. Rapid prototyping is combined with a fabrication step that we have developed to permit the incorporation of active elements, such as a peristaltic system and fluidic valves in the phantom. We have developed smart material composites that reproduce the mechanical and haptic properties, and that give ultrasound contrast indistinguishable from real organs, while permitting anatomical details to be reproduced with a mean error of as little as 500 microns.
Feedback from a major medical device company indicates that ours is a unique phantom with unprecedented accuracy for which there is a market. Within this POC grant we want to develop a complete prototype, and to demonstrate a series of medical interventions on the phantom, including endoscopic diagnostic procedures (cystoscopy and ureterorenoscopy) and endoscopic treatment procedures (laser lithotripsy). The grant will allow us to protect our know-how, identify further markets, and develop a commercialization strategy.
Overall, this project will generate the first active phantom system that permits the testing of surgical instruments and procedures, with a sizeable market potential.

Robot-assisted and minimally invasive medical procedures are impacting medical care by increasing accuracy, reducing cost, and minimizing patient discomfort and recovery times after interventions. Developers of commercial robotic surgical systems and medical device manufacturers look for realistic phantoms that can be used in place of animal experiments or cadavers to test procedures and to train medical personnel. Existing phantoms are either made from hard materials, or they lack anatomical detail, and they are mainly passive and thus unrealistic.
Here, we use recently developed fabrication know-how and expertise within our ERC-funded research to develop the first active artificial urinary tract model that includes a kidney, a bladder, and a prostate. Rapid prototyping is combined with a fabrication step that we have developed to permit the incorporation of active elements, such as a peristaltic system and fluidic valves in the phantom. We have developed smart material composites that reproduce the mechanical and haptic properties, and that give ultrasound contrast indistinguishable from real organs, while permitting anatomical details to be reproduced with a mean error of as little as 500 microns.
Feedback from a major medical device company indicates that ours is a unique phantom with unprecedented accuracy for which there is a market. Within this POC grant we want to develop a complete prototype, and to demonstrate a series of medical interventions on the phantom, including endoscopic diagnostic procedures (cystoscopy and ureterorenoscopy) and endoscopic treatment procedures (laser lithotripsy). The grant will allow us to protect our know-how, identify further markets, and develop a commercialization strategy.
Overall, this project will generate the first active phantom system that permits the testing of surgical instruments and procedures, with a sizeable market potential.

Max ERC Funding

150 000 €

Duration

Start date: 2017-03-01, End date: 2018-08-31

Project acronymACUSLABS

ProjectA new tool in drug development: mapping of compound-protein interaction using forward genetics

SummaryDevelopment of new medicines such as chemotherapeutic drugs requires a detailed understanding of their biological mechanism of action. What are the desired and undesired interactions with biological molecules? It is our goal to found a start-up company that will provide a solution to this challenge. Using novel and ground-breaking approaches we can identify target structures and interaction partners of small bioactive molecules at an unmatched and unprecedented resolution. ERC PoC funding will be essential to support our activities to identify optimal strategies and initial customers for our service.

Development of new medicines such as chemotherapeutic drugs requires a detailed understanding of their biological mechanism of action. What are the desired and undesired interactions with biological molecules? It is our goal to found a start-up company that will provide a solution to this challenge. Using novel and ground-breaking approaches we can identify target structures and interaction partners of small bioactive molecules at an unmatched and unprecedented resolution. ERC PoC funding will be essential to support our activities to identify optimal strategies and initial customers for our service.

Max ERC Funding

149 563 €

Duration

Start date: 2017-07-01, End date: 2018-12-31

Project acronymAD-HOC

ProjectArtificial Dielectrics for High-frequency On-Chip antennas

Researcher (PI)Andrea Neto

Host Institution (HI)TECHNISCHE UNIVERSITEIT DELFT

Call DetailsProof of Concept (PoC), PC1, ERC-2015-PoC

SummaryHigh-speed wireless communication and automotive radars are two applications with huge social and market potentials that can be revolutionized by the development of high-frequency (sub-terahertz) technology. Despite the recent advances in low-cost integrated circuits, the poor performance of on-chip antennas is nowadays the major bottleneck in converting the electrical signals (on-chip) into radiated ones (off-chip). For decades the problem of “surface waves” has prevented the efficient use of radiators on chip.
The AD-HOC project aims at exploiting the breakthrough technology of Artificial Dielectric (AD) layers as the solution to the surface-wave problem of High-frequency On-Chip antennas. The processes necessary to micro-fabricate AD layers will be optimized with the goal of achieving reliable manufacturing, while offering design flexibility at low costs. This will allow the wide exploitation of the AD layers, as they can be used by industrial technology providers as add-on components to at least double the efficiency of their integrated circuit front ends.
By overcoming the fundamental limitation of integrated antennas, AD layers have high potential to become a “standard” component in all future car-safety and wireless-communication devices. The AD-HOC project will bring this innovative technology to a pre-demonstration stage to strengthen commercialization and scaling-up opportunities.

High-speed wireless communication and automotive radars are two applications with huge social and market potentials that can be revolutionized by the development of high-frequency (sub-terahertz) technology. Despite the recent advances in low-cost integrated circuits, the poor performance of on-chip antennas is nowadays the major bottleneck in converting the electrical signals (on-chip) into radiated ones (off-chip). For decades the problem of “surface waves” has prevented the efficient use of radiators on chip.
The AD-HOC project aims at exploiting the breakthrough technology of Artificial Dielectric (AD) layers as the solution to the surface-wave problem of High-frequency On-Chip antennas. The processes necessary to micro-fabricate AD layers will be optimized with the goal of achieving reliable manufacturing, while offering design flexibility at low costs. This will allow the wide exploitation of the AD layers, as they can be used by industrial technology providers as add-on components to at least double the efficiency of their integrated circuit front ends.
By overcoming the fundamental limitation of integrated antennas, AD layers have high potential to become a “standard” component in all future car-safety and wireless-communication devices. The AD-HOC project will bring this innovative technology to a pre-demonstration stage to strengthen commercialization and scaling-up opportunities.

Max ERC Funding

150 000 €

Duration

Start date: 2016-09-01, End date: 2018-02-28

Project acronymAD-VIP

ProjectAlzheimer’s disease and AAV9: Use of a virus-based delivery system for vectored immunoprophylaxis in dementia.

Researcher (PI)MATTHEW GUY HOLT

Host Institution (HI)VIB

Call DetailsProof of Concept (PoC), PC1, ERC-2015-PoC

SummaryAlzheimer’s disease (AD) is the most common form of dementia in the Western World, representing an economic and social cost of billions of euros a year. Given the changing demographics of society, these costs will only increase over the coming decades.
Amyloid plaques, composed of amyloid beta peptide (Abeta), are a defining characteristic of AD. Evidence now suggests that Abeta is central to disease pathogenesis due to its toxicity, which leads to cell loss and eventual cognitive decline. Abeta is generated by proteolytic cleavage of amyloid precursor protein, a process that involves the protein BACE1.
Knock-down of BACE1 is sufficient to prevent amyloid pathology and cognitive deficits in transgenic mouse models of AD, so BACE1 is an attractive target for therapeutic intervention. Although many small molecule inhibitors of BACE1 have been developed, many have problems with imperfect selectivity, posing a substantial risk for off-target toxicity in vivo. In contrast, antibody-based therapeutics provide an attractive alternative given their excellent molecular selectivity. However, the success of antibody therapies in AD is limited by the blood brain barrier, which limits antibody entry into the brain from the systemic circulation.
Recent studies have shown that adeno-associated virus serotype 9 (AAV9) effectively crosses the blood brain barrier. Here, we propose evaluating the use of AAV9 as a delivery system for a highly specific and potent inhibitory nanobody targeted against BACE1 as a treatment for AD.

Alzheimer’s disease (AD) is the most common form of dementia in the Western World, representing an economic and social cost of billions of euros a year. Given the changing demographics of society, these costs will only increase over the coming decades.
Amyloid plaques, composed of amyloid beta peptide (Abeta), are a defining characteristic of AD. Evidence now suggests that Abeta is central to disease pathogenesis due to its toxicity, which leads to cell loss and eventual cognitive decline. Abeta is generated by proteolytic cleavage of amyloid precursor protein, a process that involves the protein BACE1.
Knock-down of BACE1 is sufficient to prevent amyloid pathology and cognitive deficits in transgenic mouse models of AD, so BACE1 is an attractive target for therapeutic intervention. Although many small molecule inhibitors of BACE1 have been developed, many have problems with imperfect selectivity, posing a substantial risk for off-target toxicity in vivo. In contrast, antibody-based therapeutics provide an attractive alternative given their excellent molecular selectivity. However, the success of antibody therapies in AD is limited by the blood brain barrier, which limits antibody entry into the brain from the systemic circulation.
Recent studies have shown that adeno-associated virus serotype 9 (AAV9) effectively crosses the blood brain barrier. Here, we propose evaluating the use of AAV9 as a delivery system for a highly specific and potent inhibitory nanobody targeted against BACE1 as a treatment for AD.

Max ERC Funding

150 000 €

Duration

Start date: 2016-12-01, End date: 2018-05-31

Project acronymADAPTEM

ProjectAdaptive transmission electron microscopy: development of a programmable phase plate

Researcher (PI)Johan VERBEECK

Host Institution (HI)UNIVERSITEIT ANTWERPEN

Call DetailsProof of Concept (PoC), ERC-2017-PoC

SummaryAdaptive optics, the technology to dynamically program the phase of optical waves has sparked an avalanche of scientific discoveries and innovations in light optics applications. Nowadays, the phase of optical waves can be dynamically programmed providing research on exotic optical beams and unprecedented control over the performance of optical instruments. Although electron waves carry many similarities in comparison to their optical counterparts, a generic programmable phase plate for electrons is still missing. This project aims at developing a prototype of a programmable electrostatic phase plate that allows the user to freely change the phase of electron waves and demonstrate it to potential licensees for further upscaling and introduction to the market. The target of this POC project is the realization of a tunable easy-to-use 5x5-pixel prototype that will demonstrate the potential of adaptive optics in electron microscopy. Its realization will be based on lithographic technology to allow for future upscaling. It is expected that such a phase plate can dramatically increase the information obtained at a given electron dose, limiting the detrimental effects of beam damage that currently hinders the use of electron microscopy in e.g. life sciences. As such, it has the potential to disrupt the electron microscopy market with novel applications while at the same time reducing cost and complexity and increasing the potential for fully automated instruments.

Adaptive optics, the technology to dynamically program the phase of optical waves has sparked an avalanche of scientific discoveries and innovations in light optics applications. Nowadays, the phase of optical waves can be dynamically programmed providing research on exotic optical beams and unprecedented control over the performance of optical instruments. Although electron waves carry many similarities in comparison to their optical counterparts, a generic programmable phase plate for electrons is still missing. This project aims at developing a prototype of a programmable electrostatic phase plate that allows the user to freely change the phase of electron waves and demonstrate it to potential licensees for further upscaling and introduction to the market. The target of this POC project is the realization of a tunable easy-to-use 5x5-pixel prototype that will demonstrate the potential of adaptive optics in electron microscopy. Its realization will be based on lithographic technology to allow for future upscaling. It is expected that such a phase plate can dramatically increase the information obtained at a given electron dose, limiting the detrimental effects of beam damage that currently hinders the use of electron microscopy in e.g. life sciences. As such, it has the potential to disrupt the electron microscopy market with novel applications while at the same time reducing cost and complexity and increasing the potential for fully automated instruments.

SummaryThe ERC StG project UNICON (Project ID 202984) was completed in July 2013. The goal of UNICON was to develop new adaptive finite element methods for computer simulation of fluid-structure interaction, in particular for problems involving turbulent flow. Simulation of turbulent flow is an outstanding computational challenge, where the UNICON project made significant progress beyond the state of the art. The scientific results of the UNICON project include a new theoretical and methodological framework, and a computer implementation of the methods as open source software, published as part of the FEniCS project, co-founded by the PI (Hoffman) in 2003. FEniCS is today a world leading open source software for computer simulation based on differential equations, with an estimated 50 000 downloads per year, and the PI today leads the PRACE Tier-0 project FEniCS-HPC, in which algorithms and software are developed for the most powerful supercomputers in Europe. Compared to competing simulation software, free as well as commercial, UNICON computational technology has proven to exhibit unique features with respect to accuracy and efficiency.
The idea of this ERC PoC project is to commercialize the UNICON simulation technology. In particular, ADAPTIVE targets civil (non-military) industry, with a focus on subsonic fluid dynamics. The strategy is to deliver services and products tailored to each customer, from deliverance of a simulation result, to education and support for integration of the simulation tools in the workflow of a customer.

The ERC StG project UNICON (Project ID 202984) was completed in July 2013. The goal of UNICON was to develop new adaptive finite element methods for computer simulation of fluid-structure interaction, in particular for problems involving turbulent flow. Simulation of turbulent flow is an outstanding computational challenge, where the UNICON project made significant progress beyond the state of the art. The scientific results of the UNICON project include a new theoretical and methodological framework, and a computer implementation of the methods as open source software, published as part of the FEniCS project, co-founded by the PI (Hoffman) in 2003. FEniCS is today a world leading open source software for computer simulation based on differential equations, with an estimated 50 000 downloads per year, and the PI today leads the PRACE Tier-0 project FEniCS-HPC, in which algorithms and software are developed for the most powerful supercomputers in Europe. Compared to competing simulation software, free as well as commercial, UNICON computational technology has proven to exhibit unique features with respect to accuracy and efficiency.
The idea of this ERC PoC project is to commercialize the UNICON simulation technology. In particular, ADAPTIVE targets civil (non-military) industry, with a focus on subsonic fluid dynamics. The strategy is to deliver services and products tailored to each customer, from deliverance of a simulation result, to education and support for integration of the simulation tools in the workflow of a customer.

Max ERC Funding

146 897 €

Duration

Start date: 2015-04-01, End date: 2016-09-30

Project acronymAdaSmartRes

ProjectAdapter for a commercial grade camera or a smart phone to perform depth resolved imaging

Researcher (PI)Adrian PODOLEANU

Host Institution (HI)UNIVERSITY OF KENT

Call DetailsProof of Concept (PoC), PC1, ERC-2016-PoC

SummaryThe proposal refers to a patented adapter that can transform a commercial grade digital camera or the camera in a smart phone into a depth resolved imaging instrument. Several adapters will be assembled, making use of optical coherence tomography (OCT) technology protected by some other of PI’s patents. The activity takes advantage of recent progress in commercial grade cameras in terms of their modes of operation as well as in terms of parameters of their devices, such as sensitivity and speed of their photodetector arrays.
Three versions of low cost functional OCT systems will be assembled as proof of concepts responding to needs of three possible markets that can be addressed by such an adapter: 1. En-face depth resolved, high transversal resolution microscope; 2. Fast cross sectioning imager. 3. Swept source volumetric analyser.
Industrial input comes from a company involved in professional eye imaging systems, a company already selling adapters for smart phones to perform medical imaging, a company specialised in digital photographic equipment and a company efficient in prototyping photonics equipment and handling medical images. Clinical input is provided by two specialists in the two highest potential medical imaging markets of the adapter serving ophthalmology and ear, nose and throat speciality.

The proposal refers to a patented adapter that can transform a commercial grade digital camera or the camera in a smart phone into a depth resolved imaging instrument. Several adapters will be assembled, making use of optical coherence tomography (OCT) technology protected by some other of PI’s patents. The activity takes advantage of recent progress in commercial grade cameras in terms of their modes of operation as well as in terms of parameters of their devices, such as sensitivity and speed of their photodetector arrays.
Three versions of low cost functional OCT systems will be assembled as proof of concepts responding to needs of three possible markets that can be addressed by such an adapter: 1. En-face depth resolved, high transversal resolution microscope; 2. Fast cross sectioning imager. 3. Swept source volumetric analyser.
Industrial input comes from a company involved in professional eye imaging systems, a company already selling adapters for smart phones to perform medical imaging, a company specialised in digital photographic equipment and a company efficient in prototyping photonics equipment and handling medical images. Clinical input is provided by two specialists in the two highest potential medical imaging markets of the adapter serving ophthalmology and ear, nose and throat speciality.

Max ERC Funding

149 300 €

Duration

Start date: 2017-06-01, End date: 2018-11-30

Project acronymADDABU

ProjectAutomated detection of damage to buildings

Researcher (PI)Luc VAN GOOL

Host Institution (HI)EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH

Call DetailsProof of Concept (PoC), ERC-2017-PoC

SummaryHail and storm damages represent the most often occurring cases for building insurance companies. Currently, the damage is estimated by an insurance expert, visiting the damaged building and drafting a report. Researchers at the Computer Vision Lab at ETH Zurich joined forces with business and sales people, spinning out the company Casalva, to strongly reduce such costs via automated image analysis. The idea is that the insurers’ clients upload photos of the damages, which will then be analyzed automatically by a computer. This involves computer vision technologies – grounded in the ERC project VarCity – to recognize the damaged building structures and to analyze the corresponding textures as to assess the extent of the damage and the estimated costs for its repair. Cutting costs is not the only consideration, as the fast assessment of damages improves customer satisfaction and prevents the occurrence of additional damages because of a delayed repair (like water leaking before repair). Such follow-on damages are estimated to be 20% of overall costs on average and are therefore far from negligible. Guaranteeing a short term response currently is a major issue, as a single storm may affect thousands of buildings. Processing times tend to stretch out due to the peak in cases following such extreme weather events. Over half of hail storm damage cases concern facade structures. The VarCity project produced methods to automatically parse facades into such structures, and to select the best way to describe their textures. These will be refined to optimally deal with the application area. The remaining technical developments and risk mitigations will be funded through other means (a Swiss project that has already been submitted), while this Proof-of-Concept project will focus on equally important aspects like market analysis, development of a corporate identity and graphical house style for the Casalva spin-off, that has been created but should now get market introduction.

Hail and storm damages represent the most often occurring cases for building insurance companies. Currently, the damage is estimated by an insurance expert, visiting the damaged building and drafting a report. Researchers at the Computer Vision Lab at ETH Zurich joined forces with business and sales people, spinning out the company Casalva, to strongly reduce such costs via automated image analysis. The idea is that the insurers’ clients upload photos of the damages, which will then be analyzed automatically by a computer. This involves computer vision technologies – grounded in the ERC project VarCity – to recognize the damaged building structures and to analyze the corresponding textures as to assess the extent of the damage and the estimated costs for its repair. Cutting costs is not the only consideration, as the fast assessment of damages improves customer satisfaction and prevents the occurrence of additional damages because of a delayed repair (like water leaking before repair). Such follow-on damages are estimated to be 20% of overall costs on average and are therefore far from negligible. Guaranteeing a short term response currently is a major issue, as a single storm may affect thousands of buildings. Processing times tend to stretch out due to the peak in cases following such extreme weather events. Over half of hail storm damage cases concern facade structures. The VarCity project produced methods to automatically parse facades into such structures, and to select the best way to describe their textures. These will be refined to optimally deal with the application area. The remaining technical developments and risk mitigations will be funded through other means (a Swiss project that has already been submitted), while this Proof-of-Concept project will focus on equally important aspects like market analysis, development of a corporate identity and graphical house style for the Casalva spin-off, that has been created but should now get market introduction.

Max ERC Funding

143 750 €

Duration

Start date: 2017-09-01, End date: 2018-08-31

Project acronymADMIRE

ProjectA holographic microscope for the immersive exploration of augmented micro-reality

Researcher (PI)Roberto DI LEONARDO

Host Institution (HI)UNIVERSITA DEGLI STUDI DI ROMA LA SAPIENZA

Call DetailsProof of Concept (PoC), ERC-2017-PoC

SummaryVirtual reality, augmented reality and mixed reality are beginning to transform the way we explore and acquire information from the macroscopic world around us. At the same time, recent advances in holographic microscopy are providing new tools for the 3D imaging of physical and biological phenomena occurring at the micron scale. Project ADMIRE will combine this two emerging technologies into the first prototype of an AugmenteD MIcro-REality system for the immersive exploration and the quantitative analysis of three-dimensional processes at the micron scale.
The core of the proposed system will be the three-axis holographic microscope (3DHM) developed within the ERC Project SMART to investigate fast 3D dynamics of swimming bacteria.
ADMIRE project will transform 3DHM from a laboratory technique, targeted to a specific application and operated by highly specialised researchers into a general purpose instrument composed of a compact add-on module for commercial optical microscopes and a virtual reality interface allowing for a direct and intuitive use. Through the ADMIRE Holographic Microscope (ADMIRE-HM) the user will be “shrunk” a million times and virtually sent into a live 3D reconstruction of the real microscopic world contained in the glass slide. There he will find himself surrounded by micro-particles or moving cells that could be inspected from multiple directions and characterized by shape parameters (e.g. size, volume, aspect-ratio) or dynamical features (e.g. flagellar motility, sedimentation velocity, transport in a flow) obtained by means of simple and direct gestures.
The expected outcome of the project is to bring to a development stage TRL 6-7 a technology that could change the way we experience the microscopic world in basic research, biomedical applications and education.

Virtual reality, augmented reality and mixed reality are beginning to transform the way we explore and acquire information from the macroscopic world around us. At the same time, recent advances in holographic microscopy are providing new tools for the 3D imaging of physical and biological phenomena occurring at the micron scale. Project ADMIRE will combine this two emerging technologies into the first prototype of an AugmenteD MIcro-REality system for the immersive exploration and the quantitative analysis of three-dimensional processes at the micron scale.
The core of the proposed system will be the three-axis holographic microscope (3DHM) developed within the ERC Project SMART to investigate fast 3D dynamics of swimming bacteria.
ADMIRE project will transform 3DHM from a laboratory technique, targeted to a specific application and operated by highly specialised researchers into a general purpose instrument composed of a compact add-on module for commercial optical microscopes and a virtual reality interface allowing for a direct and intuitive use. Through the ADMIRE Holographic Microscope (ADMIRE-HM) the user will be “shrunk” a million times and virtually sent into a live 3D reconstruction of the real microscopic world contained in the glass slide. There he will find himself surrounded by micro-particles or moving cells that could be inspected from multiple directions and characterized by shape parameters (e.g. size, volume, aspect-ratio) or dynamical features (e.g. flagellar motility, sedimentation velocity, transport in a flow) obtained by means of simple and direct gestures.
The expected outcome of the project is to bring to a development stage TRL 6-7 a technology that could change the way we experience the microscopic world in basic research, biomedical applications and education.

Max ERC Funding

150 000 €

Duration

Start date: 2017-11-01, End date: 2019-04-30

Project acronymAI-CU

ProjectAutomated Improvement of Continuous User interfaces

Researcher (PI)BART GERBEN DE BOER

Host Institution (HI)VRIJE UNIVERSITEIT BRUSSEL

Call DetailsProof of Concept (PoC), ERC-2017-PoC

SummaryWe propose to develop two tools for creating, in a systematic way, better user interfaces based on continuous, non-symbolic actions, such as swipes on a touch screen, 3-D motions with a hand-held device, or breath patterns in a user interface for otherwise paralyzed patients. The tools are based on two experimental/computational techniques developed in the ABACUS project: iterated learning and social coordination.
In iterated learning, sets of signals produced by one user are learned and reproduced by another user. The reproductions are then in turn learned by the next user. In the ABACUS project, it has been shown that this results in more learnable sets of signals. We propose to show how this can be applied to creating learnable and usable signals in a systematic way when design a user interface for a device that allows continuous actions.
In social coordination, it has been shown that signals become simplified and more abstract when people communicate over an extended period of time. The ABACUS project has developed techniques to detect and quantify this. We propose to show how these can be used for a user interface that adapts to its user. This will allow novice users to use more extended and therefore more learnable versions of actions, while the system adapts when users become more adept at using the interface and reduce their actions. Because the system is adaptive, the user is not constrained in how they do this.
Concretely, we propose to implement these two tools, investigate how they can be used optimally and advertise them to interested companies, starting with ones with which we have contact, but extending our network at the start of the project through a business case development. In order to disseminate the results we propose to involve a user committee and organize one or more workshops.

We propose to develop two tools for creating, in a systematic way, better user interfaces based on continuous, non-symbolic actions, such as swipes on a touch screen, 3-D motions with a hand-held device, or breath patterns in a user interface for otherwise paralyzed patients. The tools are based on two experimental/computational techniques developed in the ABACUS project: iterated learning and social coordination.
In iterated learning, sets of signals produced by one user are learned and reproduced by another user. The reproductions are then in turn learned by the next user. In the ABACUS project, it has been shown that this results in more learnable sets of signals. We propose to show how this can be applied to creating learnable and usable signals in a systematic way when design a user interface for a device that allows continuous actions.
In social coordination, it has been shown that signals become simplified and more abstract when people communicate over an extended period of time. The ABACUS project has developed techniques to detect and quantify this. We propose to show how these can be used for a user interface that adapts to its user. This will allow novice users to use more extended and therefore more learnable versions of actions, while the system adapts when users become more adept at using the interface and reduce their actions. Because the system is adaptive, the user is not constrained in how they do this.
Concretely, we propose to implement these two tools, investigate how they can be used optimally and advertise them to interested companies, starting with ones with which we have contact, but extending our network at the start of the project through a business case development. In order to disseminate the results we propose to involve a user committee and organize one or more workshops.

Max ERC Funding

150 000 €

Duration

Start date: 2018-06-01, End date: 2019-11-30

Project acronymAIDViC

ProjectAntibiotic intracellular delivery via virus-like carriers

Researcher (PI)Giuseppe BATTAGLIA

Host Institution (HI)UNIVERSITY COLLEGE LONDON

Call DetailsProof of Concept (PoC), PC1, ERC-2016-PoC

SummaryTaking inspiration from natural carriers, such as viruses, a new technology has been developed in
our laboratories part of an ongoing ERC starting grant project, Molecular Engineering of Virus-like
Carriers (MEViC). We created synthetic viruses using polymers and thus safer materials. They are
able of delivering high payload of specific drugs into cells with no detrimental effect. While testing for
anticancer therapies, we identified a synthetic virus capable of targeting almost exclusively
macrophages. We performed preliminary work showing that this can be successfully applied to
deliver antibiotics to rid of intracellular pathogens. This has now open a completely new possibility
whereas we can expand our technology for the treatment of several infections as well as to contribute
to the ongoing efforts in tackling antibiotic resistance.

Taking inspiration from natural carriers, such as viruses, a new technology has been developed in
our laboratories part of an ongoing ERC starting grant project, Molecular Engineering of Virus-like
Carriers (MEViC). We created synthetic viruses using polymers and thus safer materials. They are
able of delivering high payload of specific drugs into cells with no detrimental effect. While testing for
anticancer therapies, we identified a synthetic virus capable of targeting almost exclusively
macrophages. We performed preliminary work showing that this can be successfully applied to
deliver antibiotics to rid of intracellular pathogens. This has now open a completely new possibility
whereas we can expand our technology for the treatment of several infections as well as to contribute
to the ongoing efforts in tackling antibiotic resistance.

Max ERC Funding

149 062 €

Duration

Start date: 2017-07-01, End date: 2018-12-31

Project acronymAIM

ProjectAdaptive Imaging Microscopy

Researcher (PI)Michel Verhaegen

Host Institution (HI)TECHNISCHE UNIVERSITEIT DELFT

Call DetailsProof of Concept (PoC), PC1, ERC-2016-PoC

SummaryThe project has a goal of starting up a small business producing highly special customizable microscope systems for biomedical research. Microscopic imaging is one of the major drivers of the progress in biomedical and life sciences. The development of novel concepts, addressing the challenges of advanced optical microscopy, represents the front line of scientific research. Modern microscopes are not purely optical devices anymore. They have developed into complex integrated systems, combining optics, mechanics, electronics, feedback control systems, and image processing Many novel concepts of modern microscopy, while very interesting for research, still have to prove the commercial profitability. Such developments can be effectively addressed by start-up companies with a goal of either custom development, production and service of these advanced systems, or development and selling the IP to a larger player.
The major goal of this proposal is the creation of the first commercial optical microscope, the performance of which depends completely on the adaptive optics feedback controls. To prove the feasibility of this approach, we select a highly attractive technical concept of adaptive light sheet microscope, developed in our group in the framework of the ERC project. In this aspect, our development relates to ordinary microscope system in the same way as “fly by wire” airplane relates to an old-fashioned one.
Our contribution in the development of instrumentation for biomedical research will bring a positive impact on our knowledge about the nature and ourselves, the quality of life and life expectation of the population. Our proposal addresses the largest societal challenge of Europe: the healthcare. Our instrument will contribute to the understanding of complex diseases and support the greying population to stay healthy and self-supportive for extended period of time.

The project has a goal of starting up a small business producing highly special customizable microscope systems for biomedical research. Microscopic imaging is one of the major drivers of the progress in biomedical and life sciences. The development of novel concepts, addressing the challenges of advanced optical microscopy, represents the front line of scientific research. Modern microscopes are not purely optical devices anymore. They have developed into complex integrated systems, combining optics, mechanics, electronics, feedback control systems, and image processing Many novel concepts of modern microscopy, while very interesting for research, still have to prove the commercial profitability. Such developments can be effectively addressed by start-up companies with a goal of either custom development, production and service of these advanced systems, or development and selling the IP to a larger player.
The major goal of this proposal is the creation of the first commercial optical microscope, the performance of which depends completely on the adaptive optics feedback controls. To prove the feasibility of this approach, we select a highly attractive technical concept of adaptive light sheet microscope, developed in our group in the framework of the ERC project. In this aspect, our development relates to ordinary microscope system in the same way as “fly by wire” airplane relates to an old-fashioned one.
Our contribution in the development of instrumentation for biomedical research will bring a positive impact on our knowledge about the nature and ourselves, the quality of life and life expectation of the population. Our proposal addresses the largest societal challenge of Europe: the healthcare. Our instrument will contribute to the understanding of complex diseases and support the greying population to stay healthy and self-supportive for extended period of time.

Max ERC Funding

149 998 €

Duration

Start date: 2017-05-01, End date: 2018-10-31

Project acronymAirKit

ProjectCitizen Sense Air Monitoring Kit

Researcher (PI)Jennifer Chloe GABRYS

Host Institution (HI)GOLDSMITHS' COLLEGE

Call DetailsProof of Concept (PoC), ERC-2017-PoC

SummaryIn January 2013, the five-year ERC funded project Citizen Sense was launched, investigating the role of low-cost and digital monitoring technologies in facilitating and organising new types of environmental engagement. This proposal brings together a comprehensive citizen-sensing toolkit for users to undertake air quality monitoring that realises the social and environmental potential of these technologies. With the benefit of five years of intensive and cutting-edge research, the Citizen Sense research project is exceptionally well positioned to develop an AirKit, thereby bridging the gap between our research and the early stages of innovation in order to realise the innovation potential of the project. Our research pioneers new strategies of citizen-led monitoring and data analysis that join up hardware and software developments along with social innovations in order to produce an AirKit toolkit that has the potential to revolutionise community monitoring infrastructures and practices. This PoC will help to establish the viability of the AirKit, to refine and address technical issues, and to consolidate the overall direction of the AirKit.

In January 2013, the five-year ERC funded project Citizen Sense was launched, investigating the role of low-cost and digital monitoring technologies in facilitating and organising new types of environmental engagement. This proposal brings together a comprehensive citizen-sensing toolkit for users to undertake air quality monitoring that realises the social and environmental potential of these technologies. With the benefit of five years of intensive and cutting-edge research, the Citizen Sense research project is exceptionally well positioned to develop an AirKit, thereby bridging the gap between our research and the early stages of innovation in order to realise the innovation potential of the project. Our research pioneers new strategies of citizen-led monitoring and data analysis that join up hardware and software developments along with social innovations in order to produce an AirKit toolkit that has the potential to revolutionise community monitoring infrastructures and practices. This PoC will help to establish the viability of the AirKit, to refine and address technical issues, and to consolidate the overall direction of the AirKit.

SummaryThis proposal draws on the extensive technical developments of Ad-G 323041 LOCATE to commercialise the know-how to build a low-cost aircraft with integrated aerial survey, filming and tracking technology capable of operating in low-infrastructure environments. These requirements are common to many applications and there is currently no affordable off-the-shelf solution. Our product is unique, providing a technologically-advanced integrated data collection system controlled by a single pilot. Modular technology enables buyers to select options relevant to their own operation and minimise start-up costs. With operating costs of approximately €30/hour, our product will make sophisticated aerial survey, filming and tracking accessible to researchers, NGOs, government and commercial operators, delivering impact through high-resolution, high-quality information at low cost for infrastructure survey (eg pipeline, rail/cabling and flood plain survey) and conservation (habitat change, wildlife density), land and habitat management (national parks, game reserves). This aerial survey platform fills a market niche between drones (limited by payload and range) and commercial operations (high cost, require infrastructure, lack of flexibility). We will: DOCUMENT the structural modifications and specification for fitting out the aircraft with the equipment payload specified; REFINE the on-board systems set-up and mission planning system; DOCUMENT the options for modular on-board technology; DEVELOP a costing model for building, equipping, fitting out and operating the aircraft and licensing of IP; UNDERTAKE market analysis and research and communicate with potential suppliers and users; PREPARE a comprehensive portfolio for uptake by potential commercial partners. The project team includes three aviation/industry members experienced in bringing innovative technologies to this market.

This proposal draws on the extensive technical developments of Ad-G 323041 LOCATE to commercialise the know-how to build a low-cost aircraft with integrated aerial survey, filming and tracking technology capable of operating in low-infrastructure environments. These requirements are common to many applications and there is currently no affordable off-the-shelf solution. Our product is unique, providing a technologically-advanced integrated data collection system controlled by a single pilot. Modular technology enables buyers to select options relevant to their own operation and minimise start-up costs. With operating costs of approximately €30/hour, our product will make sophisticated aerial survey, filming and tracking accessible to researchers, NGOs, government and commercial operators, delivering impact through high-resolution, high-quality information at low cost for infrastructure survey (eg pipeline, rail/cabling and flood plain survey) and conservation (habitat change, wildlife density), land and habitat management (national parks, game reserves). This aerial survey platform fills a market niche between drones (limited by payload and range) and commercial operations (high cost, require infrastructure, lack of flexibility). We will: DOCUMENT the structural modifications and specification for fitting out the aircraft with the equipment payload specified; REFINE the on-board systems set-up and mission planning system; DOCUMENT the options for modular on-board technology; DEVELOP a costing model for building, equipping, fitting out and operating the aircraft and licensing of IP; UNDERTAKE market analysis and research and communicate with potential suppliers and users; PREPARE a comprehensive portfolio for uptake by potential commercial partners. The project team includes three aviation/industry members experienced in bringing innovative technologies to this market.

Summary"Acute inflammatory processes are associated with infections as well as autoimmune flares at the basis of a variety of human diseases. While the molecular components and the logic of pro-inflammatory program are relatively well understood, less is known about the molecular mechanism of resolution, governing the termination of inflammatory responses. In the course of carrying out the i-FIVE ERC grant project plan, we identified a novel, secreted, soluble enzyme as a negative regulator of pro-inflammatory immunity receptors. Here we propose a defined and focused set of measures aimed at obtaining solid evidence for therapeutic feasibility of this novel biological agent in resolving inflammatory processes as well as for the securing of intellectual property. The AIRSHIP workplan proposes to obtain enough purified, soluble, endotoxin-free, active and glycosylated protein material to execute two critical tests, one monitoring the inflammatory response in human cells, and one addressing beneficiary effects in a lung murine infection model. Armed with such a successful proof of concept package and having strategically positioned and secured our intellectual property rights we would be determined to embark into an ambitious commercialization initiative."

"Acute inflammatory processes are associated with infections as well as autoimmune flares at the basis of a variety of human diseases. While the molecular components and the logic of pro-inflammatory program are relatively well understood, less is known about the molecular mechanism of resolution, governing the termination of inflammatory responses. In the course of carrying out the i-FIVE ERC grant project plan, we identified a novel, secreted, soluble enzyme as a negative regulator of pro-inflammatory immunity receptors. Here we propose a defined and focused set of measures aimed at obtaining solid evidence for therapeutic feasibility of this novel biological agent in resolving inflammatory processes as well as for the securing of intellectual property. The AIRSHIP workplan proposes to obtain enough purified, soluble, endotoxin-free, active and glycosylated protein material to execute two critical tests, one monitoring the inflammatory response in human cells, and one addressing beneficiary effects in a lung murine infection model. Armed with such a successful proof of concept package and having strategically positioned and secured our intellectual property rights we would be determined to embark into an ambitious commercialization initiative."

Max ERC Funding

150 000 €

Duration

Start date: 2012-12-01, End date: 2013-11-30

Project acronymALEX

ProjectALgorithms EXposed. Investigating Automated Personalization and Filtering for Research and Activism

Researcher (PI)Stefania MILAN

Host Institution (HI)UNIVERSITEIT VAN AMSTERDAM

Call DetailsProof of Concept (PoC), ERC-2018-PoC

SummaryPersonalization algorithms—filtering content on the basis of someone's profile—increasingly mediate the web experience of users. By forging a specific reality for each individual, they silently shape customized 'information diets': in other words, they determine which news, opinions and rumors users are exposed to. Restricting users’ possibilities, they ultimately infringe on their agency. As exposed by the recent Cambridge Analytica scandal, they are supported by questionable data sharing practices at the core of the business models of the social media industry. Yet, personalization algorithms are proprietary and thus remain inaccessible to end users. The few experiments auditing these algorithms rely on data provided by platform companies themselves. They are highly technical, hardly scalable, and fail to put social media users in the driver seat. The ALgorithms EXposed (ALEX) project aims at unmasking the functioning of personalization algorithms on social media platforms, taking Facebook as a test case. It is 'data activism' in practice, as it uses publicly available data for awareness raising and citizen empowerment. ALEX will pursue five goals: 1) software development and stabilization, building on the alpha version of facebook.tracking.exposed (fbtrex), a working prototype of a browser extension analyzing the outcomes of Facebook's News Feed algorithms; 2) the release of two spin-off products building on fbtrex, namely AudIT, enabling researchers to do expert analysis on algorithmic biases, and RealityCheck, allowing users to monitor their own social media consumption patterns; 3) testing the technical feasibility of adapting the ALEX approach to analyze algorithmic personalization on other platforms such as Twitter and Google; 4) the design and organization of data literacy modules on algorithmic personalization, and 5) the launch of a consultancy service to promote tool take-up and the future sustainability of the project.

Personalization algorithms—filtering content on the basis of someone's profile—increasingly mediate the web experience of users. By forging a specific reality for each individual, they silently shape customized 'information diets': in other words, they determine which news, opinions and rumors users are exposed to. Restricting users’ possibilities, they ultimately infringe on their agency. As exposed by the recent Cambridge Analytica scandal, they are supported by questionable data sharing practices at the core of the business models of the social media industry. Yet, personalization algorithms are proprietary and thus remain inaccessible to end users. The few experiments auditing these algorithms rely on data provided by platform companies themselves. They are highly technical, hardly scalable, and fail to put social media users in the driver seat. The ALgorithms EXposed (ALEX) project aims at unmasking the functioning of personalization algorithms on social media platforms, taking Facebook as a test case. It is 'data activism' in practice, as it uses publicly available data for awareness raising and citizen empowerment. ALEX will pursue five goals: 1) software development and stabilization, building on the alpha version of facebook.tracking.exposed (fbtrex), a working prototype of a browser extension analyzing the outcomes of Facebook's News Feed algorithms; 2) the release of two spin-off products building on fbtrex, namely AudIT, enabling researchers to do expert analysis on algorithmic biases, and RealityCheck, allowing users to monitor their own social media consumption patterns; 3) testing the technical feasibility of adapting the ALEX approach to analyze algorithmic personalization on other platforms such as Twitter and Google; 4) the design and organization of data literacy modules on algorithmic personalization, and 5) the launch of a consultancy service to promote tool take-up and the future sustainability of the project.

Max ERC Funding

149 922 €

Duration

Start date: 2018-12-01, End date: 2020-02-29

Project acronymALGOA

ProjectNovel algorithm for treatment planning of patients with osteoarthritis

Researcher (PI)Rami Kristian KORHONEN

Host Institution (HI)ITA-SUOMEN YLIOPISTO

Call DetailsProof of Concept (PoC), PC1, ERC-2016-PoC

SummaryOsteoarthritis (OA) is a common joint disease affecting over 40 million Europeans. Most common consequences of OA are pain, disability and social isolation. What is alarming, the number of patients will increase 50% in developed countries during the next 20 years. Moreover, the economic costs of OA are considerable since 1) direct healthcare (hospital admissions, medical examinations, drug therapy, etc.) and 2) productivity costs due to reduced performance while at work and absence from work have been estimated to be between 1% and 2.5% of the gross domestic product (GDP) in Western countries.
We have developed an algorithm that is able to predict the progression of OA for overweight subjects while healthy subjects do not develop OA. When employed in clinical use, preventive and personalised treatments can be started before clinically significant symptoms are observed. This marks a major breakthrough in improving the life quality of OA patients and patients prone to OA. Our discovery will directly lead to longer working careers and lesser absence from work, and will result subsequently increased productivity. Moreover, the patients are expected to live longer due to reduced disability and social isolation.
Moreover, the discovery provides economic long-term relief for the health care system, which is burdened by increasing geriatric population and stringent economic environment. With our tool, as an example, by eliminating 25% of medical examinations annually due to overweight or obesity in Finland (150.000 patients), we estimate to decrease annual direct costs by 140M€ and indirect costs by 185M€.
In the PoC project we will carry out technical proof-of-concept and perform pre-commercialisation actions to shorten the time to market. The ultimate goal after the project is to develop our innovation towards a software product, aiding the OA diagnostics in hospitals and having commercialisation potential amongst medical device companies.

Osteoarthritis (OA) is a common joint disease affecting over 40 million Europeans. Most common consequences of OA are pain, disability and social isolation. What is alarming, the number of patients will increase 50% in developed countries during the next 20 years. Moreover, the economic costs of OA are considerable since 1) direct healthcare (hospital admissions, medical examinations, drug therapy, etc.) and 2) productivity costs due to reduced performance while at work and absence from work have been estimated to be between 1% and 2.5% of the gross domestic product (GDP) in Western countries.
We have developed an algorithm that is able to predict the progression of OA for overweight subjects while healthy subjects do not develop OA. When employed in clinical use, preventive and personalised treatments can be started before clinically significant symptoms are observed. This marks a major breakthrough in improving the life quality of OA patients and patients prone to OA. Our discovery will directly lead to longer working careers and lesser absence from work, and will result subsequently increased productivity. Moreover, the patients are expected to live longer due to reduced disability and social isolation.
Moreover, the discovery provides economic long-term relief for the health care system, which is burdened by increasing geriatric population and stringent economic environment. With our tool, as an example, by eliminating 25% of medical examinations annually due to overweight or obesity in Finland (150.000 patients), we estimate to decrease annual direct costs by 140M€ and indirect costs by 185M€.
In the PoC project we will carry out technical proof-of-concept and perform pre-commercialisation actions to shorten the time to market. The ultimate goal after the project is to develop our innovation towards a software product, aiding the OA diagnostics in hospitals and having commercialisation potential amongst medical device companies.

Max ERC Funding

150 000 €

Duration

Start date: 2018-01-01, End date: 2019-06-30

Project acronymALKVAX

ProjectMarket potentials of ALK vaccination as a new strategy for the cure of ALK positive tumors such as lymphoma, lung carcinoma and neuroblastoma

Researcher (PI)Roberto CHIARLE

Host Institution (HI)UNIVERSITA DEGLI STUDI DI TORINO

Call DetailsProof of Concept (PoC), PC1, ERC-2012-PoC

SummaryALK positive cancer such as Anaplastic Large Cell Lymphoma (ALCL), Non small Cell Lung Carcinoma (NSCLC) and neuroblastoma are important cancers of children and adults, currently treated with standard chemotherapy and radiotherapy, with unpredicatable and poor results, in particular in the case of NSCLC and neuroblastoma. In August 2011, the US Food and Drug Administration (FDA) had an accelerated approval of a novel drug (called Crizotinib) to treat NSCLC that express abnormal ALK protein. Phase II and III clinical trials are ongoing to test the same drug in ALCL and neuroblastoma. However, it is now clear that the treatment with Crizotinib has a good initial efficacy and response, but the cancer inevitably relapses because of the occurrence of drug resistance. This resistance is due to selection of ALK point mutants that no longer bind the inhibitor. New drugs to tame the resistant cells will be probably developed in the future (as happened for Gleevec and second and third generation of BCR-ABL inhibitors), but it is expected that again resistance will emerge.
As part of a research conducted under an ERC Starting Grat, we developed a new therapy for ALK positive ALCL, NSCLC and neuroblastoma based on the generation of a potent and specific anti-tumor response based on the development of an ALK-targeted immune response. This specific anti-ALK immune response is achieved by an anti-ALK vaccination in preclinical mouse models of ALCL and NSCLC. Now, in this Proof-of-Concept grant, we propose to take the next steps to move our invention toward a clinical application in human patients, by testing GLP formulations of the vaccine, its potential toxic effects and by searching the market for companies interested in its development and commercialization. Our goal is to understand and finalize the best strategy to move this experimental therapy to the market and generate a partnership with a pharma company.

ALK positive cancer such as Anaplastic Large Cell Lymphoma (ALCL), Non small Cell Lung Carcinoma (NSCLC) and neuroblastoma are important cancers of children and adults, currently treated with standard chemotherapy and radiotherapy, with unpredicatable and poor results, in particular in the case of NSCLC and neuroblastoma. In August 2011, the US Food and Drug Administration (FDA) had an accelerated approval of a novel drug (called Crizotinib) to treat NSCLC that express abnormal ALK protein. Phase II and III clinical trials are ongoing to test the same drug in ALCL and neuroblastoma. However, it is now clear that the treatment with Crizotinib has a good initial efficacy and response, but the cancer inevitably relapses because of the occurrence of drug resistance. This resistance is due to selection of ALK point mutants that no longer bind the inhibitor. New drugs to tame the resistant cells will be probably developed in the future (as happened for Gleevec and second and third generation of BCR-ABL inhibitors), but it is expected that again resistance will emerge.
As part of a research conducted under an ERC Starting Grat, we developed a new therapy for ALK positive ALCL, NSCLC and neuroblastoma based on the generation of a potent and specific anti-tumor response based on the development of an ALK-targeted immune response. This specific anti-ALK immune response is achieved by an anti-ALK vaccination in preclinical mouse models of ALCL and NSCLC. Now, in this Proof-of-Concept grant, we propose to take the next steps to move our invention toward a clinical application in human patients, by testing GLP formulations of the vaccine, its potential toxic effects and by searching the market for companies interested in its development and commercialization. Our goal is to understand and finalize the best strategy to move this experimental therapy to the market and generate a partnership with a pharma company.

SummaryThe goal of this PoC proposal is to boost the creation of a start-up (AllYours) targeting both Internet users as well as small to medium companies (SME) offering full-fledged personalization in notification systems. The Web is now all about users; they are the greediest bandwidth consumers, the ultimate deciders of which applications are actually adopted and also the most prolific content generators. While social networks have taken off at an unexpected scale and speed, Web navigation has radically changed to the point that notification is taking over search: many users now navigate through the links they discover rather than explicit search operations. Yet, users get quickly overwhelmed with the huge amount of information in a click range. For such notification systems to be truly useful, they should be personalized depending on the user activity, operations, posts, interests. Yet, personalization poses several issues such as scalability (it is expensive to store a large amount of information per user) and privacy (users are more and more reluctant to give away their preferences to large companies). At the same time, SMEs are struggling to provide fully personalized services given the expertise and amount of resources such algorithms require.
AllYours is an implicit instant item recommender providing personalization in the notification process without requiring explicit subscriptions to feeds or interests. They only let the system know whether they like the items received or not (eg like/dislike button). In addition, users personal data are stored on their own machine, leaving the space to provide a wide spectrum of privacy guarantees while enabling cross application benefits. Behind the scene, AllYours provides each user with a live social network of participants sharing similar interests, called an implicit social network. AllYours come in two different flavors: (1) Enterprise-AllYours provides a scalable notification and recommendation system targeting all SMEs operating Web content editors & ecommerce sites (2) P2P-AllYours provides a fully decentralized solution without requiring users to ever reveal their private preferences through a clever obfuscation mechanism.

The goal of this PoC proposal is to boost the creation of a start-up (AllYours) targeting both Internet users as well as small to medium companies (SME) offering full-fledged personalization in notification systems. The Web is now all about users; they are the greediest bandwidth consumers, the ultimate deciders of which applications are actually adopted and also the most prolific content generators. While social networks have taken off at an unexpected scale and speed, Web navigation has radically changed to the point that notification is taking over search: many users now navigate through the links they discover rather than explicit search operations. Yet, users get quickly overwhelmed with the huge amount of information in a click range. For such notification systems to be truly useful, they should be personalized depending on the user activity, operations, posts, interests. Yet, personalization poses several issues such as scalability (it is expensive to store a large amount of information per user) and privacy (users are more and more reluctant to give away their preferences to large companies). At the same time, SMEs are struggling to provide fully personalized services given the expertise and amount of resources such algorithms require.
AllYours is an implicit instant item recommender providing personalization in the notification process without requiring explicit subscriptions to feeds or interests. They only let the system know whether they like the items received or not (eg like/dislike button). In addition, users personal data are stored on their own machine, leaving the space to provide a wide spectrum of privacy guarantees while enabling cross application benefits. Behind the scene, AllYours provides each user with a live social network of participants sharing similar interests, called an implicit social network. AllYours come in two different flavors: (1) Enterprise-AllYours provides a scalable notification and recommendation system targeting all SMEs operating Web content editors & ecommerce sites (2) P2P-AllYours provides a fully decentralized solution without requiring users to ever reveal their private preferences through a clever obfuscation mechanism.

SummaryBy the end of the 4th year of the ERC Advanced grant, the PI has set up the basis of a unique procedure to perform optical coherence tomography (OCT) that is similar in outcome to time domain interferometry but has all advantages of spectral domain interferometry in terms of speed and sensitivity. The new method of OCT, termed as Master/Slave (MS), is characterised by several advantages: direct production of an en-face OCT image, tolerance to dispersion that allows MS-OCT to achieve the theoretical limit of axial resolution and sensitivity that can be tailored for no hardware and time cost, with the axial resolution. By excellence, the Master/Slave OCT method delivers en-face views direct, allowing lower cost hardware and faster provision of en-face slicing and visualisation. An essential advantage is that of parallel processing, that makes MS-OCT, ideally suited to novel parallel optical configurations and graphic processing units (GPU). These advantages can substantially increase the speed in providing volumes of the tissue, making the new OCT method superior to all other methods on the market. The POC support will help advance the MS-OCT closer to commercialisation. Four market strategies are identified with immediate products for the first two. OCT add-on modules, equipped with MS software, for: A. OCT developers, to accelerate their research and B. OCT developers that can modify existing commercial OCT systems, by making them accomplish the MS protocol. The module to be assembled and assessed for commercialisation will also pave the way to two more strategies: C. Companies already selling OCT systems on dedicated markets, where specialised agreements will widen the market and even D. A full OCT system created by the new company, an ultimate outcome that requires investment, based on revenue acquired by selling the add-on modules.

By the end of the 4th year of the ERC Advanced grant, the PI has set up the basis of a unique procedure to perform optical coherence tomography (OCT) that is similar in outcome to time domain interferometry but has all advantages of spectral domain interferometry in terms of speed and sensitivity. The new method of OCT, termed as Master/Slave (MS), is characterised by several advantages: direct production of an en-face OCT image, tolerance to dispersion that allows MS-OCT to achieve the theoretical limit of axial resolution and sensitivity that can be tailored for no hardware and time cost, with the axial resolution. By excellence, the Master/Slave OCT method delivers en-face views direct, allowing lower cost hardware and faster provision of en-face slicing and visualisation. An essential advantage is that of parallel processing, that makes MS-OCT, ideally suited to novel parallel optical configurations and graphic processing units (GPU). These advantages can substantially increase the speed in providing volumes of the tissue, making the new OCT method superior to all other methods on the market. The POC support will help advance the MS-OCT closer to commercialisation. Four market strategies are identified with immediate products for the first two. OCT add-on modules, equipped with MS software, for: A. OCT developers, to accelerate their research and B. OCT developers that can modify existing commercial OCT systems, by making them accomplish the MS protocol. The module to be assembled and assessed for commercialisation will also pave the way to two more strategies: C. Companies already selling OCT systems on dedicated markets, where specialised agreements will widen the market and even D. A full OCT system created by the new company, an ultimate outcome that requires investment, based on revenue acquired by selling the add-on modules.

Max ERC Funding

149 917 €

Duration

Start date: 2015-11-01, End date: 2017-04-30

Project acronymANALYTICS

ProjectAll-electrical analytic platform for digital fluidics

Researcher (PI)Denys MAKAROV

Host Institution (HI)HELMHOLTZ-ZENTRUM DRESDEN-ROSSENDORF EV

Call DetailsProof of Concept (PoC), ERC-2017-PoC

SummaryProspective biosensing technologies will need to tackle the grand challenges arising from the global demographic changes. Among the most crucial tasks is the monitoring of food and environmental quality as well as the medical diagnosis. Digital fluidics offers vast advantages in performing these tasks relying on tiny containers with reacting biochemical species and allowing massively parallelized assays and high throughput screening using optical detection approaches.
I envision that adding not-optical detectors, which electrically probe the analyte responses, will provide a source of new but complementary information, obtained in a label-free and contactless manner. Hence, these all-electric platforms enable monitoring the kinetics of chemical reactions in lab-on-chip format, as well as take over auxiliary tasks, e.g. indexing, counting of droplets, flow monitoring.
In frame of the ERC project SMaRT, my team developed a unique detection platform -millifluidic resonance detector- that inductively couples to an analyte and assesses its physico-chemical properties. The unique selling points are (i) non-invasiveness to analyte, (ii) unnecessity of a transparent fluidic channel, (iii) cost efficiency and (iv) portability.
Implementing the input from the partner companies, here I aim to reach the commercialization stage pursuing a number of key milestones, i.e. enhance the screening throughput, realize a platform independent of external electronic devices, provide a temperature stabilization of the response, and develop the app.
Societal benefits: We demonstrated that the device provides an access to the metabolic activity of living organisms in droplets. This is way beyond the capabilities of the state-of-the-art optical detection. With this feature, the device can address the issue of increasing antibiotic resistance of bacteria and thus help to optimize the antibiotic policy in hospitals and households and to test new drugs in a time- and cost-efficient way.

Prospective biosensing technologies will need to tackle the grand challenges arising from the global demographic changes. Among the most crucial tasks is the monitoring of food and environmental quality as well as the medical diagnosis. Digital fluidics offers vast advantages in performing these tasks relying on tiny containers with reacting biochemical species and allowing massively parallelized assays and high throughput screening using optical detection approaches.
I envision that adding not-optical detectors, which electrically probe the analyte responses, will provide a source of new but complementary information, obtained in a label-free and contactless manner. Hence, these all-electric platforms enable monitoring the kinetics of chemical reactions in lab-on-chip format, as well as take over auxiliary tasks, e.g. indexing, counting of droplets, flow monitoring.
In frame of the ERC project SMaRT, my team developed a unique detection platform -millifluidic resonance detector- that inductively couples to an analyte and assesses its physico-chemical properties. The unique selling points are (i) non-invasiveness to analyte, (ii) unnecessity of a transparent fluidic channel, (iii) cost efficiency and (iv) portability.
Implementing the input from the partner companies, here I aim to reach the commercialization stage pursuing a number of key milestones, i.e. enhance the screening throughput, realize a platform independent of external electronic devices, provide a temperature stabilization of the response, and develop the app.
Societal benefits: We demonstrated that the device provides an access to the metabolic activity of living organisms in droplets. This is way beyond the capabilities of the state-of-the-art optical detection. With this feature, the device can address the issue of increasing antibiotic resistance of bacteria and thus help to optimize the antibiotic policy in hospitals and households and to test new drugs in a time- and cost-efficient way.

Host Institution (HI)THE PROVOST, FELLOWS, FOUNDATION SCHOLARS & THE OTHER MEMBERS OF BOARD OF THE COLLEGE OF THE HOLY & UNDIVIDED TRINITY OF QUEEN ELIZABETH NEAR DUBLIN

Call DetailsProof of Concept (PoC), ERC-2017-PoC

SummaryOsteoarthritis (OA), the most common form of arthritis, is a serious disease of the joints affecting nearly 10% of the population worldwide. The onset of OA has been associated with defects to articular cartilage that lines the bones of synovial joints. Current strategies to treat articular cartilage defects are ineffective and/or prohibitively expensive. The aim of ANCHOR is to develop and commercialise a new medicinal product for articular cartilage regeneration that recruits endogenous bone marrow derived stem cells into an extracellular matrix derived scaffold anchored to the subchondral bone by 3D printed polymeric supports. By recruiting endogenous cells into a supporting scaffold, ANCHOR will obviate the need for pre-seeding scaffolds with cells prior to implantation into cartilage defects, thereby dramatically reducing the cost and complexity of the repair procedure. It will also overcome the need for suturing of a scaffold into a cartilage defect, which is a very time consuming and technically challenging surgical procedure. Finally, the inherent chondro-inductivity of the cartilage ECM derived scaffolds developed by the applicant will maximise the potential for hyaline cartilage regeneration. The project will leverage the applicants extensive experience in ECM derived biomaterials and 3D printing to develop a new product with significant commercial potential. The impact of ANCHOR will be multi-faceted: it will transform how damaged joints are treated by orthopaedic surgeons, it will create economic value through the commercialization of IP, and most importantly it will improve patient experience and their long-term health and well-being.

Osteoarthritis (OA), the most common form of arthritis, is a serious disease of the joints affecting nearly 10% of the population worldwide. The onset of OA has been associated with defects to articular cartilage that lines the bones of synovial joints. Current strategies to treat articular cartilage defects are ineffective and/or prohibitively expensive. The aim of ANCHOR is to develop and commercialise a new medicinal product for articular cartilage regeneration that recruits endogenous bone marrow derived stem cells into an extracellular matrix derived scaffold anchored to the subchondral bone by 3D printed polymeric supports. By recruiting endogenous cells into a supporting scaffold, ANCHOR will obviate the need for pre-seeding scaffolds with cells prior to implantation into cartilage defects, thereby dramatically reducing the cost and complexity of the repair procedure. It will also overcome the need for suturing of a scaffold into a cartilage defect, which is a very time consuming and technically challenging surgical procedure. Finally, the inherent chondro-inductivity of the cartilage ECM derived scaffolds developed by the applicant will maximise the potential for hyaline cartilage regeneration. The project will leverage the applicants extensive experience in ECM derived biomaterials and 3D printing to develop a new product with significant commercial potential. The impact of ANCHOR will be multi-faceted: it will transform how damaged joints are treated by orthopaedic surgeons, it will create economic value through the commercialization of IP, and most importantly it will improve patient experience and their long-term health and well-being.

SummaryThe technology validation was successfully completed indicating a great commercial potential, and the innovative and inventive aspects of the assay platform are now covered by the filed priority European Patent Office (EPO) patent applications. Validated glycoprofiling of the proteins now uses lectins in a format, fully compatible with clinical PSA assay kits. This PoC grant focuses on 1. Pre-clinical retrospective validation of the early stage biomarker of prostate cancer (PCa) and 2. Commercialisation of the PCa diagnostics kit. Pre-clinical (60 human serum samples) is ongoing and retrospective validation study (450 human serum samples) of the assay will be performed by statistical analysis using a receiver operating characteristic (ROC) curve. The PoC describes all steps, which have been developed so far and all necessary steps, which need to be done for retrospective validation study, product development and commercialisation through our newly incorporated start-up Glycanostics Ltd. (www.glycanostics.com). We will provide PCa diagnostic test resulting in a second opinion to guide the right decision if the biopsy is needed. This will avoid the needless and unreliable biopsies and in the future rival an inaccurate PSA testing.

The technology validation was successfully completed indicating a great commercial potential, and the innovative and inventive aspects of the assay platform are now covered by the filed priority European Patent Office (EPO) patent applications. Validated glycoprofiling of the proteins now uses lectins in a format, fully compatible with clinical PSA assay kits. This PoC grant focuses on 1. Pre-clinical retrospective validation of the early stage biomarker of prostate cancer (PCa) and 2. Commercialisation of the PCa diagnostics kit. Pre-clinical (60 human serum samples) is ongoing and retrospective validation study (450 human serum samples) of the assay will be performed by statistical analysis using a receiver operating characteristic (ROC) curve. The PoC describes all steps, which have been developed so far and all necessary steps, which need to be done for retrospective validation study, product development and commercialisation through our newly incorporated start-up Glycanostics Ltd. (www.glycanostics.com). We will provide PCa diagnostic test resulting in a second opinion to guide the right decision if the biopsy is needed. This will avoid the needless and unreliable biopsies and in the future rival an inaccurate PSA testing.

Host Institution (HI)UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN

Call DetailsProof of Concept (PoC), ERC-2017-PoC

SummaryWater-stress in an increasing global problem and solutions such as water recycling and seawater desalination are now becoming a necessary part of the water infrastructure. The technology for the production of safe drinking is increasingly dependent on these more diverse sources and a key enabling technology is membrane filtration. While membrane system are effective, the operating costs of such systems are hampered by fouling which increases the energy requirement for process operation. The unique idea of this Proof of Concept is to develop an electrospun nanostructured membrane which can be integrated into water filtration technologies. The unique method of fabrication will produce an inherently antibacterial and antibiofouling surface in a one-step process, cutting the number of manufacturing steps. This concept, when deployed commercially is expected to dramatically reduce the operating costs of membrane processes for water treatment. The commercialisation route of the product will be through the patent protection and the licensing of the technology with a view to rapid commercialisation.

Water-stress in an increasing global problem and solutions such as water recycling and seawater desalination are now becoming a necessary part of the water infrastructure. The technology for the production of safe drinking is increasingly dependent on these more diverse sources and a key enabling technology is membrane filtration. While membrane system are effective, the operating costs of such systems are hampered by fouling which increases the energy requirement for process operation. The unique idea of this Proof of Concept is to develop an electrospun nanostructured membrane which can be integrated into water filtration technologies. The unique method of fabrication will produce an inherently antibacterial and antibiofouling surface in a one-step process, cutting the number of manufacturing steps. This concept, when deployed commercially is expected to dramatically reduce the operating costs of membrane processes for water treatment. The commercialisation route of the product will be through the patent protection and the licensing of the technology with a view to rapid commercialisation.

Max ERC Funding

148 805 €

Duration

Start date: 2017-10-01, End date: 2019-03-31

Project acronymAngioResist

ProjectCoordinated Development of Inhibitors and Biomarkers for Resistance to Antiangiogenics in Cancer - AngioResist

Researcher (PI)Oriol CASANOVAS CASANOVAS

Host Institution (HI)INSTITUT CATALA D'ONCOLOGIA

Call DetailsProof of Concept (PoC), PC1, ERC-2015-PoC

SummaryMany anti-angiogenic drugs are clinically used in several types of cancer to block angiogenesis, impair tumor growth, progression and dissemination. Nevertheless, clinical trials report emergence of resistance to treatment and a failure in long-lasting effects of these therapies. To date, resistant patients do not currently have any established, proven alternative therapeutic possibility and the medical field is moving towards a careful selection of subgroups or subtypes of patients that have to be treated with each one of the available second-line targeted drugs. For this relevant unmet medical need, many laboratories and pharmaceutical companies have focused on developing new biomarkers and new drugs to fight anti-angiogenic resistance, but up to date, there is no proven established biomarker or method to predict which patient’s tumor is resistant to antiangiogenic therapies and which drug is capable of blocking this resistance to therapy.
AngioResist PoC aims at solving the existing patient selection gap in the treatment of cancer that is therapeutically resistant to antiangiogenic drugs. Based on data generated from our ERC project and two filed European Patent applications, AngioResist PoC will transform the acquired basic knowledge into an Innovation project, to validate a novel biomarker of response/resistance to antiangiogenics together with a new inhibitor for the treatment of these selected patients. The project will coordinately perform the preclinical phases of development of the drug compound and the biomarker, with the final aim of licensing them both to a selected partner during the clinical phases. Together with our licensee, we aim at the final distribution of a therapeutic drug that will be delivered with a biomarker kit for the selection and treatment of cancer patients resistant to antiangiogenic drugs.

Many anti-angiogenic drugs are clinically used in several types of cancer to block angiogenesis, impair tumor growth, progression and dissemination. Nevertheless, clinical trials report emergence of resistance to treatment and a failure in long-lasting effects of these therapies. To date, resistant patients do not currently have any established, proven alternative therapeutic possibility and the medical field is moving towards a careful selection of subgroups or subtypes of patients that have to be treated with each one of the available second-line targeted drugs. For this relevant unmet medical need, many laboratories and pharmaceutical companies have focused on developing new biomarkers and new drugs to fight anti-angiogenic resistance, but up to date, there is no proven established biomarker or method to predict which patient’s tumor is resistant to antiangiogenic therapies and which drug is capable of blocking this resistance to therapy.
AngioResist PoC aims at solving the existing patient selection gap in the treatment of cancer that is therapeutically resistant to antiangiogenic drugs. Based on data generated from our ERC project and two filed European Patent applications, AngioResist PoC will transform the acquired basic knowledge into an Innovation project, to validate a novel biomarker of response/resistance to antiangiogenics together with a new inhibitor for the treatment of these selected patients. The project will coordinately perform the preclinical phases of development of the drug compound and the biomarker, with the final aim of licensing them both to a selected partner during the clinical phases. Together with our licensee, we aim at the final distribution of a therapeutic drug that will be delivered with a biomarker kit for the selection and treatment of cancer patients resistant to antiangiogenic drugs.

Max ERC Funding

149 932 €

Duration

Start date: 2016-09-01, End date: 2018-02-28

Project acronymaNtHESIS

ProjectNovel heart regeneration strategies

Researcher (PI)Eldad Tzahor

Host Institution (HI)WEIZMANN INSTITUTE OF SCIENCE

Call DetailsProof of Concept (PoC), PC1, ERC-2014-PoC

SummaryHeart disease and particularly myocardial infarction, i.e. heart attack, is the leading cause of death in the Western world today. The diminished regenerative potential of the heart begins shortly after birth, when most CardioMyocytes (CMs) cease to proliferate and make a transition from hyperplastic to hypertrophic growth. The Tzahor lab has been intensively exploring novel molecules, compounds as well as the molecular mechanisms that facilitate CM cell division in the adult heart of mammals as a strategy for eliciting heart regeneration. These efforts, had led to the identification of novel compounds which significantly increased the proliferation of adult CMs. Drawing upon these findings, the aim of the aNtHESIS project is two-fold. First, to (i) validate the pre-clinical application of our two novel compounds by conducting comprehensive in-vitro and in-vivo tests in mice as well as by carrying out experiments using human CMs. The second aim is (ii) to establish the business feasibility of our cardiac regenerative therapy concept by taking the necessary steps towards the commercialization of our novel compounds, focusing on the creation of strategic alliances with key private sector companies.

Heart disease and particularly myocardial infarction, i.e. heart attack, is the leading cause of death in the Western world today. The diminished regenerative potential of the heart begins shortly after birth, when most CardioMyocytes (CMs) cease to proliferate and make a transition from hyperplastic to hypertrophic growth. The Tzahor lab has been intensively exploring novel molecules, compounds as well as the molecular mechanisms that facilitate CM cell division in the adult heart of mammals as a strategy for eliciting heart regeneration. These efforts, had led to the identification of novel compounds which significantly increased the proliferation of adult CMs. Drawing upon these findings, the aim of the aNtHESIS project is two-fold. First, to (i) validate the pre-clinical application of our two novel compounds by conducting comprehensive in-vitro and in-vivo tests in mice as well as by carrying out experiments using human CMs. The second aim is (ii) to establish the business feasibility of our cardiac regenerative therapy concept by taking the necessary steps towards the commercialization of our novel compounds, focusing on the creation of strategic alliances with key private sector companies.

Max ERC Funding

150 000 €

Duration

Start date: 2016-01-01, End date: 2017-06-30

Project acronymAnti-CSC

ProjectTargeting Cancer Stem Cells (CSC) for the development of more effective treatments to cure cancer patients

SummaryGlobal cancer market is growing at a CAGR of 6.9% with an estimated value of $81bn in 2016. Although the huge R&D investment observed in the past years in the development of new treatments, there is still lack on an effective treatment in many tumour types. In particular, the median survival for glioblastoma multiforme (GBM), a high-grade brain tumour affecting 23,000 patients a year in US and EU, is 14 months and its 5-yr survival less than 5%. It is therefore urgent to develop more effective treatments against this fatal disease.
It has been recently demonstrated that Cancer Stem Cells (CSCs) are responsible from tumour initiation, maintenance, relapse and treatment resistance, and therefore therapies targeting CSC should eradicate the tumour. Our team has discovered a molecular pathway critical in the regulation of CSC. The project presented here entails the proof of concept and pre-clinical development of a humanized antibody blocking this pathway. Our murine version of the antibody blocks CSC development in vitro by 54% and tumour recurrence in a mice model by 50%. At the end of the ERC POC project we will have a patent protected and fully humanized antibody active in vivo and in vitro and ready to enter Phase 1 clinical trials in humans to continue its commercialization process. The forecasted annual peak revenue for this therapeutic antibody is $530M with additional sales coming from line extensions in other cancer indications.
With the ERC POC project we are dramatically increasing the commercial value of the therapeutic antibody, transforming an R&D finding (CSC are critical for cancer development) into a potential new solution to patients (a therapeutic antibody targeting CSC). Hence, we are de-risking the product, advancing it through the commercialization path and creating a product and a commercial data package with a good expectative in the cancer market that is ready to be out-licensed or transferred to a spin-off previous VC investment.

Global cancer market is growing at a CAGR of 6.9% with an estimated value of $81bn in 2016. Although the huge R&D investment observed in the past years in the development of new treatments, there is still lack on an effective treatment in many tumour types. In particular, the median survival for glioblastoma multiforme (GBM), a high-grade brain tumour affecting 23,000 patients a year in US and EU, is 14 months and its 5-yr survival less than 5%. It is therefore urgent to develop more effective treatments against this fatal disease.
It has been recently demonstrated that Cancer Stem Cells (CSCs) are responsible from tumour initiation, maintenance, relapse and treatment resistance, and therefore therapies targeting CSC should eradicate the tumour. Our team has discovered a molecular pathway critical in the regulation of CSC. The project presented here entails the proof of concept and pre-clinical development of a humanized antibody blocking this pathway. Our murine version of the antibody blocks CSC development in vitro by 54% and tumour recurrence in a mice model by 50%. At the end of the ERC POC project we will have a patent protected and fully humanized antibody active in vivo and in vitro and ready to enter Phase 1 clinical trials in humans to continue its commercialization process. The forecasted annual peak revenue for this therapeutic antibody is $530M with additional sales coming from line extensions in other cancer indications.
With the ERC POC project we are dramatically increasing the commercial value of the therapeutic antibody, transforming an R&D finding (CSC are critical for cancer development) into a potential new solution to patients (a therapeutic antibody targeting CSC). Hence, we are de-risking the product, advancing it through the commercialization path and creating a product and a commercial data package with a good expectative in the cancer market that is ready to be out-licensed or transferred to a spin-off previous VC investment.